Samuel Canizales-Quinteros

Publications of Samuel Canizales-Quinteros

• Carbohydrate intake modulates the effect of the ABCA1-R230C variant on HDL cholesterol concentrations in premenopausal women.

  Authors: Sandra Romero-Hidalgo, Teresa Villarreal-Molina, Juan A González-Barrios, Samuel Canizales-Quinteros, Martha E Rodríguez-Arellano, Lucia B Yañez-Velazco, Demetrio A Bernal-Alcantara, Antonio R Villa, Barbara Antuna-Puente, Víctor Acuña-Alonzo, José L Merino-García, Hayde N Moreno-Sandoval, Alessandra Carnevale

  The Journal of nutrition. 12/2011; 142(2):278-83.

  The R230C variant of the ATP-binding cassette transporter A1 (ABCA1) gene has been consistently associated with decreased HDL-cholesterol (HDL-C) concentrations in several studies in the MexicanThe R230C variant of the ATP-binding cassette transporter A1 (ABCA1) gene has been consistently associated with decreased HDL-cholesterol (HDL-C) concentrations in several studies in the Mexican mestizo population. However, information on how diet composition modifies the effect of the ABCA1-R230C variant on HDL-C concentrations is very scarce. The aim of the present study was to analyze whether the effect of ABCA1-R230C on HDL-C concentrations is modulated by dietary factors in a nationwide population sample of 3591 adults from the National Health and Nutrition Survey conducted by the State's Employees' Social Security and Social Services Institute. All participants answered a validated questionnaire to assess health status and weekly food consumption. Fasting blood samples were drawn for biochemical analysis and DNA extraction, and the ABCA1-R230C variant was genotyped using TaqMan assays. Statistical analyses consisted of simple linear and multiple regression modeling adjusting for age, BMI, smoking, and alcohol consumption. The overall C risk allele frequency was 9.3% and the variant was significantly associated with low HDL-C concentrations in both sexes. A significant negative correlation between carbohydrate consumption and HDL-C concentrations was observed in women bearing the R230C variant (P = 0.021) and a significant gene-diet interaction was found only in premenopausal women (P = 0.037). In conclusion, the effect of the ABCA1-R230C gene variant on HDL-C concentrations is modulated by carbohydrate intake in premenopausal women. This finding may help design optimized dietary interventions according to sex and ABCA1-R230C genotype.

• A dietary pattern including nopal, chia seed, soy protein, and oat reduces serum triglycerides and glucose intolerance in patients with metabolic syndrome.

  Authors: Martha Guevara-Cruz, Armando R Tovar, Carlos A Aguilar-Salinas, Isabel Medina-Vera, Lidia Gil-Zenteno, Isaac Hernández-Viveros, Patricia López-Romero, Guillermo Ordaz-Nava, Samuel Canizales-Quinteros, Luz E Guillen Pineda, Nimbe Torres

  The Journal of nutrition. 11/2011; 142(1):64-9.

  Metabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of aMetabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of a dietary pattern (DP; soy protein, nopal, chia seed, and oat) on the biochemical variables of MetS, the AUC for glucose and insulin, glucose intolerance (GI), the relationship of the presence of certain polymorphisms related to MetS, and the response to the DP. In this randomized trial, the participants consumed their habitual diet but reduced by 500 kcal for 2 wk. They were then assigned to the placebo (P; n = 35) or DP (n = 32) group and consumed the reduced energy diet plus the P or DP beverage (235 kcal) minus the energy provided by these for 2 mo. All participants had decreases in body weight (BW), BMI, and waist circumference during the 2-mo treatment (P < 0.0001); however, only the DP group had decreases in serum TG, C-reactive protein (CRP), and AUC for insulin and GI after a glucose tolerance test. Interestingly, participants in the DP group with MetS and the ABCA1 R230C variant had a greater decrease in BW and an increase in serum adiponectin concentration after 2 mo of dietary treatment than those with the ABCA1 R230R variant. The results from this study suggest that lifestyle interventions involving specific DP for the treatment of MetS could be more effective if local foods and genetic variations of the population are considered.

• The non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 is associated with low HDL cholesterol concentrations in Mexican adults: a population based nation wide study.

  Authors: Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros, Rosalba Rojas-Martínez, Roopa Mehta, Rosario Rodriguez-Guillén, María Luisa Ordoñez-Sanchez, Laura Riba, María Teresa Tusié-Luna

  Atherosclerosis. 01/2011; 216(1):146-50.

  To search for an association between the non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 and low HDL cholesterol levels in a Mexican, population-based nation wideTo search for an association between the non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 and low HDL cholesterol levels in a Mexican, population-based nation wide survey. The 2000 National Health Survey is a cross sectional study that included individuals from 400 cities. All individuals who had a 9-12-h fasted blood sample and a DNA sample were selected (n = 1729). These cases were randomly distributed; no bias was detected for sex, education, region or socioeconomic status. The R230C variant was genotyped using TaqMan assays. In individuals with the R230C/C230C genotypes (39.03 mg/dl (36.63-41.43)) lower HDL-C levels (p < 0.001) were observed compared to those with the R230R genotype (44.7 mg/dl (43.31-46.24)). The difference remained significant after adjusting for gender, body mass index and waist circumference; the mean difference in HDL cholesterol levels between alleles was 5.73 ± 1.4 mg/dl. The magnitude of the effect was significantly greater in males. The C230 allele of ABCA1 was associated with an increased risk for hypoalphalipoproteinemia (OR 1.66 (95%CI 1.08-2.54), p < 0.05). The population attributable risk (PAR) for having hypoalphalipoproteinemia of the C230 allele of the ABCA1, after considering the confounding effect of waist circumference and gender, was 12.2% (95%CI 1.4-24.2%). The non-synonymous Arg230Cys variant of ABCA1 is associated with low levels of HDL cholesterol levels in Mexican adults. The HDL cholesterol lowering effect of the variant is greater in males. The size of the effect is greater compared to that reported for other ABCA1 variants.

• Endothelial nitric oxide synthase haplotypes are associated with preeclampsia in Maya mestizo women.

  Authors: Lizbeth Díaz-Olguín, Ramón Mauricio Coral-Vázquez, Thelma Canto-Cetina, Samuel Canizales-Quinteros, Belem Ramírez Regalado, Genny Fernández, Patricia Canto

  Disease markers. 01/2011; 31(2):83-9.

  Preeclampsia is a specific disease of pregnancy and believed to have a genetic component. The aim of this study was to investigate if three polymorphisms in eNOS or their haplotypes are associatedPreeclampsia is a specific disease of pregnancy and believed to have a genetic component. The aim of this study was to investigate if three polymorphisms in eNOS or their haplotypes are associated with preeclampsia in Maya mestizo women. A case-control study was performed where 127 preeclamptic patients and 263 controls were included. Genotyped and haplotypes for the -768T→C, intron 4 variants, Glu298Asp of eNOS were determined by PCR and real-time PCR allelic discrimination. Logistic regression analysis with adjustment for age and body mass index (BMI) was used to test for associations between genotype and preeclampsia under recessive, codominant and dominant models. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r^{2} , and haplotype analysis was conducted. Women homozygous for the Asp298 allele showed an association of preeclampsia. In addition, analysis of the haplotype frequencies revealed that the -786C-4b-Asp298 haplotype was significantly more frequent in preeclamptic patients than in controls (0.143 vs. 0.041, respectively; OR =3.01; 95% CI = 1.74-5.23; P =2.9 × 10 ^{-4} ).Despite the Asp298 genotype in a recessive model associated with the presence of preeclampsia in Maya mestizo women, we believe that in this population the -786C-4b-Asp298 haplotype is a better genetic marker.

• Association of R230C ABCA1 gene variant with low HDL-C levels and abnormal HDL subclass distribution in Mexican school-aged children.

  Authors: Teresa Flores-Dorantes, Olimpia Arellano-Campos, Rosalinda Posadas-Sánchez, Teresa Villarreal-Molina, Aida Medina-Urrutia, Sandra Romero-Hidalgo, Petra Yescas-Gómez, Oscar Pérez-Méndez, Esteban Jorge-Galarza, Teresa Tusié-Luna, Marisela Villalobos-Comparán, Leonor Jacobo-Albavera, Hugo Villamil-Ramírez, Blanca E López-Contreras, Carlos A Aguilar-Salinas, Carlos Posadas-Romero, Samuel Canizales-Quinteros

  Clinica chimica acta; international journal of clinical chemistry. 09/2010; 411(17-18):1214-7.

  The effect of ABCA1 genetic variation on HDL-C levels has been widely documented, although studies in children are scarce. We recently found a frequent non-synonymous ABCA1 variant (R230C) exclusiveThe effect of ABCA1 genetic variation on HDL-C levels has been widely documented, although studies in children are scarce. We recently found a frequent non-synonymous ABCA1 variant (R230C) exclusive to populations with Native American ancestry, associated with low HDL-C levels and other metabolic traits in adults. We genotyped R230C variant in 1253 healthy unrelated Mexican school-aged children aged 6-15 years (595 boys and 658 girls) to seek associations with HDL-C levels and other metabolic traits. HDL subclass distribution was analyzed in a subgroup of 81 age, gender and BMI-matched children. Individuals carrying the C230 allele showed a significantly lower HDL-C levels (P=2.9x10(-8)), and higher TC/HDL-C ratio, BMI, BMI z-score and percent fat mass (P=0.001, 0.049, 0.032 and 0.039, respectively). HDL size was smaller in R230C heterozygotes as compared to R230R homozygotes (P<0.05). Moreover, the proportion of HDL(2b) was lower, while the proportion of HDL(3a) and HDL(3b) particles was higher in R230C heterozygous and/or C230C homozygous individuals as compared to R230R homozygotes (P<0.05). Our data suggest that the R230C ABCA1 gene variant plays an important role in HDL-C level regulation and HDL subclass distribution in healthy Mexican school-aged children.

• Delta-sarcoglycan gene polymorphism frequency in Amerindian and Mestizo populations of Mexico.

  Authors: Rosa María Ordoñez-Razo, Samuel Canizales-Quinteros, Maricela Rodríguez-Cruz, Rosenda Peñaloza, Fernando Minauro-Sanmiguel, Thelma Canto-Cetina, Patricia Canto, Ramón Coral-Vázquez, Fabio Salamanca-Gómez

  Genetic testing and molecular biomarkers. 04/2010; 14(2):237-40.

  Mutations on the delta-sarcoglycan gene have been associated with the development of both hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy. Recently, the polymorphism c.-94C>G wasMutations on the delta-sarcoglycan gene have been associated with the development of both hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy. Recently, the polymorphism c.-94C>G was associated with HCM in Japanese patients. The aim of our study was to evaluate the frequency of c.-94C>G polymorphism in Mexican-Amerindian and Mexican-Mestizo populations. We analyzed the frequency of this polymorphism in 165 Mexican-Amerindian individuals (23 Triquis, 25 Zapotecos, 24 Mayas, 41 Nahuas, and 52 Mixtecos) and 100 unrelated Mexican-Mestizos. Allele frequencies were similar in all Amerindian groups (0.33 Triquis, 0.54 Zapotecos, 0.54 Mayas, 0.46 Nahuas, and 0.49 Mixtecos). When compared with Mexican-Mestizos, only Triquis were different (p = 0.00742). However, when comparing the total sample of the Amerindian population with the Mestizos, the difference was not significant (p = 0.12225). Allele frequencies of Mexican populations were higher than in Asians and less than African and European populations (p < 0.05). These data show that the distribution of the C allele is higher in Mexican populations studied and consequently it is necessary to define if this may be associated with genetic susceptibility for HCM in the Mexican patients.

• A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans.

  Authors: Víctor Acuña-Alonzo, Teresa Flores-Dorantes, Janine K Kruit, Teresa Villarreal-Molina, Olimpia Arellano-Campos, Tábita Hünemeier, Andrés Moreno-Estrada, Ma Guadalupe Ortiz-López, Hugo Villamil-Ramírez, Paola León-Mimila [......] Carlos A Aguilar-Salinas, Ruben Lisker, Regina S Moises, Marta Menjivar, Francisco M Salzano, William C Knowler, M Cátira Bortolini, Michael R Hayden, Leslie J Baier, Samuel Canizales-Quinteros

  Human molecular genetics. 04/2010; 19(14):2877-85.

  It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassetteIt has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 x 10(-11)) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations.

• Analysis of polymorphisms in genes (AGT, MTHFR, GPIIIa, and GSTP1) associated with hypertension, thrombophilia and oxidative stress in Mestizo and Amerindian populations of México.

  Authors: Rocio Juárez-Velázquez, Patricia Canto, Thelma Canto-Cetina, Hector Rangel-Villalobos, Haydee Rosas-Vargas, Maricela Rodríguez, Samuel Canizales-Quinteros, Ana Claudia Velázquez Wong, Rosa María Ordoñez-Razo, Guadalupe Vilchis-Dorantes, Ramón Mauricio Coral-Vázquez

  Disease markers. 01/2010; 28(5):323-31.

  Several polymorphisms related to hypertension, thrombophilia, and oxidative stress has been associated with the development of cardiovascular disease. We analyzed the frequency of M235TSeveral polymorphisms related to hypertension, thrombophilia, and oxidative stress has been associated with the development of cardiovascular disease. We analyzed the frequency of M235T angiotensinogen (AGT), A222V 5,10 methylenete-trahydrofolate reductase (MTHFR), L33P glycoprotein IIIa (GPIIIa), and I105V glutathione S-transferase P1 (GSTP1)} polymorphisms in 285 individuals belonging to Mexican-Mestizo and five Amerindian population from México, by real time PCR allelic discrimination. Allele and genotype frequencies were compared using chi square tests. All populations followed the Hardy Weinberg equilibrium for assay markers with the exception of the Triki, whose were in Hardy Weinberg dysequilibrium for the glutathione S-transferase P1 polymorphism. Interestingly, according to all the analyzed single nucleotide polymorphisms (SNPs), the Triki population was the most differentiated and homogeneous group of the six populations analyzed. A comparison of our data with those previously published for some Caucasian, Asian and Black populations showed quite significant differences. These differences were remarkable with all the Mexican populations having a lower frequency of the 105V allele of the glutathione S-transferase P1 and reduced occurrence of the 222A allele of the 5,10 methylenetetrahydrofolate reductase. Our results show the genetic diversity among different Mexican populations and with other racial groups.

• Hypoalphalipoproteinemia in populations of Native American ancestry: an opportunity to assess the interaction of genes and the environment.

  Authors: Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros, Rosalba Rojas-Martínez, Roopa Mehta, Ma Teresa Villarreal-Molina, Olimpia Arellano-Campos, Laura Riba, Francisco J Gómez-Pérez, Ma Teresa Tusié-Luna

  Current opinion in lipidology. 05/2009; 20(2):92-7.

  PURPOSE OF THIS REVIEW: Our aim is to review the environmental and genetic factors associated with hypoalphalipoproteinemia in populations of Native American ancestry. We examine the strength of thePURPOSE OF THIS REVIEW: Our aim is to review the environmental and genetic factors associated with hypoalphalipoproteinemia in populations of Native American ancestry. We examine the strength of the association and outline the population-specific genetic factors that lead to a higher susceptibilty for this condition. RECENT FINDINGS: Low HDL is the most common lipid abnormality in populations of Native American ancestry. Population-based surveys carried out in Latin America and in Mexican Americans shows that 40-60% of adults have hypoalphalipoproteinemia. The contribution of this trait to the metabolic syndrome is greater in individuals with Native American ancestry than in other ethnic groups. Several environmental factors have contributed to this phenomenon (i.e. high dietary content of carbohydrates and fat due to cultural factors and a growing incidence of obesity). In addition, results from recent genetic studies show that certain hypoalphalipoproteinemia susceptibility alleles are ethnic specific for Native Americans. The variant R230C of the ATP-binding cassette transporter subfamily A member 1 gene (ABC-A1) is common among mestizos (10.9% in Mexican mestizos) and its presence has a significant negative effect on HDL cholesterol levels (-4.2%). An additional noteworthy finding is that the R230C variant appears to be specific for the Amerindian populations. Its allele frequency is 0.28 in Mayans, 0.214 in Purepechas, 0.203 in Yaquis and 0.179 among Teenek. In contrast, the C230 allele has not been found in African, European, Chinese or South Asian populations. SUMMARY: The assessment of the genetic and environmental determinants of hypoalphalipoproteinemia in populations of Native American origin provides an opportunity to assess the population-specific interactions between genes and the environment

• High adiponectin concentrations are associated with the metabolically healthy obese phenotype.

  Authors: Carlos A Aguilar-Salinas, Eduardo García-García, Lorena Robles, Daniela Riaño, Doris Georgina Ruiz-Gomez, Ana Cristina García-Ulloa, Marco A Melgarejo, Margarita Zamora, Luz E Guillen Pineda, Roopa Mehta, Samuel Canizales-Quinteros, Ma Teresa Tusie Luna, Francisco J Gómez-Pérez

  The Journal of clinical endocrinology and metabolism. 09/2008;

  Context: In the ob/ob mice, keeping adiponectin concentrations in the physiological range (through overexpression of this gene in the adipose tissue) results in expansion of fat mass and protectionContext: In the ob/ob mice, keeping adiponectin concentrations in the physiological range (through overexpression of this gene in the adipose tissue) results in expansion of fat mass and protection against metabolic co-morbidities. Objective: To test in humans whether plasma adiponectin levels, similar to those found in lean subjects, are associated with the metabolically healthy obese phenotype. Design and Setting: A cross-sectional analysis of a cohort of obese and non-obese subjects aged 18-70 years. A medical history was taken and glucose, plasma lipids and total adiponectin were measured. Participants: We studied 189 men and 527 women. The majority were obese (n=470, 65.6%). The metabolically healthy obese phenotype was found in 38 men and 133 women. This is defined as a body mass index (BMI) above 30 kg/m(2) plus HDL cholesterol >/= 40 mg/dl in the absence of type 2 diabetes and arterial hypertension. Results: Twenty percent of the cases with a BMI above 40 kg/m(2) had adiponectin concentrations above the median value of normal BMI subjects. Adiponectin levels above 12.49 mg/l in obese women (OR 3.02 (95% CI 1.95-4.67, p<0.001) and above 8.07 mg/l in obese men (OR 2.14 (95%CI 1.1-4.06, p=0.01) increased the probability of being metabolically healthy. The association remained significant (beta 0.673 +/- 0.205, p<0.001) in a logistic regression model (r(2)=0.25, p<0.001) after controlling for the confounding effect of age, insulin and waist circumference. Conclusions: Certain obese individuals have adiponectin levels similar to those found in normal BMI subjects; this is associated with the metabolically healthy obese phenotype.

• The FTO Gene Is Associated With Adulthood Obesity in the Mexican Population.

  Authors: Marisela Villalobos-Comparán, M Teresa Flores-Dorantes, M Teresa Villarreal-Molina, Maricela Rodríguez-Cruz, Ana C García-Ulloa, Lorena Robles, Adriana Huertas-Vázquez, Nubia Saucedo-Villarreal, Mardia López-Alarcón, Fausto Sánchez-Muñoz [......] Sandra Romero-Hidalgo, Doris G Ruiz-Gómez, Daniela Riaño-Barros, Miguel F Herrera, Francisco J Gómez-Pérez, Philippe Froguel, Eduardo García-García, M Teresa Tusié-Luna, Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros

  Obesity (Silver Spring, Md.). 08/2008;

  Common polymorphisms in the fat mass and obesity-associated gene (FTO) have shown strong association with obesity in several populations. In the present study, we explored the association of FTO geneCommon polymorphisms in the fat mass and obesity-associated gene (FTO) have shown strong association with obesity in several populations. In the present study, we explored the association of FTO gene polymorphisms with obesity and other biochemical parameters in the Mexican population. We also assessed FTO gene expression levels in adipose tissue of obese and nonobese individuals. The study comprised 788 unrelated Mexican-Mestizo individuals and 31 subcutaneous fat tissue biopsies from lean and obese women. FTO single-nucleotide polymorphisms (SNPs) rs9939609, rs1421085, and rs17817449 were associated with obesity, particularly with class III obesity, under both additive and dominant models (P = 0.0000004 and 0.000008, respectively). These associations remained significant after adjusting for admixture (P = 0.000003 and 0.00009, respectively). Moreover, risk alleles showed a nominal association with lower insulin levels and homeostasis model assessment of B-cell function (HOMA-B), and with higher homeostasis model assessment of insulin sensitivity (HOMA-S) only in nonobese individuals (P (dom) = 0.031, 0.023, and 0.049, respectively). FTO mRNA levels were significantly higher in subcutaneous fat tissue of class III obese individuals than in lean individuals (P = 0.043). Risk alleles were significantly associated with higher FTO expression in the class III obesity group (P = 0.047). In conclusion, FTO is a major risk factor for obesity (particularly class III) in the Mexican-Mestizo population, and is upregulated in subcutaneous fat tissue of obese individuals.Obesity (2008) doi:10.1038/oby.2008.367.

• Methylenetetrahydrofolate reductase C677T and glutathione S-transferase P1 A313G are associated with a reduced risk of preeclampsia in Maya-Mestizo women.

  Authors: Patricia Canto, Thelma Canto-Cetina, Rocio Juárez-Velázquez, Haydee Rosas-Vargas, Héctor Rangel-Villalobos, Samuel Canizales-Quinteros, Ana C Velázquez-Wong, María T Villarreal-Molina, Genny Fernández, Ramón Coral-Vázquez

  Hypertension research : official journal of the Japanese Society of Hypertension. 06/2008; 31(5):1015-9.

  Preeclampsia, a common complication of pregnancy, is characterized by elevated blood pressure and proteinuria developing after 20 weeks' gestational age. Susceptibility to this syndrome is believedPreeclampsia, a common complication of pregnancy, is characterized by elevated blood pressure and proteinuria developing after 20 weeks' gestational age. Susceptibility to this syndrome is believed to have a genetic component. The aim of this study was to investigate whether or not the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and glutathione S-transferase P1 (GSTP1) A313G polymorphisms are associated with preeclampsia in Maya-Mestizo women. A case-control study was performed, in which 125 preeclamptic patients and 274 healthy controls were genotyped for the MTHFR C677T and GSTP1 A313G polymorphisms by real-time PCR allelic discrimination. Allele and genotype frequencies were compared using the chi2 tests. The MTHFR 677T allele and the 677TT genotype were significantly more frequent in the controls, suggesting an association with a decreased risk of preeclampsia (p = 0.017 and p = 0.007, respectively). Similarly, GSTP1 313GG/GC genotypes and the G allele were more frequent in controls, showing a significant association with reduced risk of preeclampsia (p = 0.008 and p = 0.013, respectively). Our results suggest, for the first time, that the MTHFR 677T and GSTP1 313G polymorphisms confer a significantly decreased risk of developing preeclampsia in the Mexican Maya-Mestizo population.

• Association of the ATP-binding cassette transporter A1 R230C variant with early-onset type 2 diabetes in a Mexican population.

  Authors: M Teresa Villarreal-Molina, M Teresa Flores-Dorantes, Olimpia Arellano-Campos, Marisela Villalobos-Comparan, Maricela Rodríguez-Cruz, Angel Miliar-García, Adriana Huertas-Vazquez, Marta Menjivar, Sandra Romero-Hidalgo, Niels H Wacher, M Teresa Tusie-Luna, Miguel Cruz, Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros

  Diabetes. 02/2008; 57(2):509-13.

  OBJECTIVE: The ATP-binding cassette transporter A1 (ABCA1) R230C variant is associated with low HDL cholesterol levels, obesity, and the metabolic syndrome in Mexican-Mestizos. Because a pivotal roleOBJECTIVE: The ATP-binding cassette transporter A1 (ABCA1) R230C variant is associated with low HDL cholesterol levels, obesity, and the metabolic syndrome in Mexican-Mestizos. Because a pivotal role for ABCA1 in pancreatic beta-cell function was recently observed in the mouse model, we assessed the association of this variant with type 2 diabetes in this population. RESEARCH DESIGN AND METHODS: The initial group included 446 unrelated Mexican individuals: 244 with type 2 diabetes aged 20-69 years (121 with onset </=45 years), and 202 nondiabetic control subjects aged >50 years. An independent study group included 242 type 2 diabetic case subjects and 225 control subjects with similar characteristics. RESULTS: R230C/C230C genotypes were significantly more frequent in type 2 diabetic individuals (24.6%) than in control subjects (11.4%) in the initial study group (OR 2.501; P = 0.001). After stratifying by age at diagnosis, the association was significant only in the early-onset group (age at diagnosis </=45 years) (OR 3.776, P = 3.3 x 10(-6)). Both associations remained significant after adjusting for admixture (P = 0.0008 and P = 8.1 x 10(-6), respectively). Similar trends were observed in the independent study group, and the combined analysis of both populations showed a highly significant association of the R230C variant with type 2 diabetes, particularly with that of early onset (P = 7.6 x 10(-6) and 9.4 x 10(-8), respectively). CONCLUSIONS: The R230C ABCA1 variant is associated with type 2 diabetes, particularly of early onset, in the Mexican-Mestizo population.

• The ATP-binding cassette transporter subfamily A member 1 (ABC-A1) and type 2 diabetes: an association beyond HDL cholesterol.

  Authors: Carlos A Aguilar-Salinas, Ivette Cruz-Bautista, Roopa Mehta, Ma T Villarreal-Molina, Francisco J G Pérez, Ma T Tusié-Luna, Samuel Canizales-Quinteros

  Current diabetes reviews. 12/2007; 3(4):264-7.

  Recent findings from several groups demonstrate that ABC-A1 participates in the pathogenesis of the metabolic syndrome and type 2 diabetes. A variant of the ABC-A1 gene (R230C) is associated with theRecent findings from several groups demonstrate that ABC-A1 participates in the pathogenesis of the metabolic syndrome and type 2 diabetes. A variant of the ABC-A1 gene (R230C) is associated with the metabolic syndrome and its co-morbidities in Mexicans. Its presence is associated with an increased risk for obesity, the metabolic syndrome and type 2 diabetes. R230C is found exclusively in Amerindian and Amerindian-derived populations. Moreover, animal models confirm the participation of ABC-A1 in the pathogenesis of diabetes. Mice lacking AbcA1 specifically in beta cells had glucose intolerance at 8 weeks of age. The absence of ABC-A1 led to cholesterol accumulation within the beta cell plasma membrane, suggesting that cholesterol may play a role in the insulin secretory pathway. In conclusion, ABC-A1 may be more than a determinant of HDL-cholesterol. It may provide a link between components of the metabolic syndrome and atherosclerosis.

• SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome.

  Authors: Argelia Medeiros-Domingo, Toshihiko Kaku, David J Tester, Pedro Iturralde Torres, Ajit Itty, Bin Ye, Carmen Valdivia, Kazuo Ueda, Samuel Canizales-Quinteros, Maria Teresa Tusié-Luna, Jonathan C Makielski, Michael J Ackerman

  Circulation. 08/2007; 116(2):134-42.

  BACKGROUND: Congenital long-QT syndrome (LQTS) is potentially lethal secondary to malignant ventricular arrhythmias and is caused predominantly by mutations in genes that encode cardiac ion channels.BACKGROUND: Congenital long-QT syndrome (LQTS) is potentially lethal secondary to malignant ventricular arrhythmias and is caused predominantly by mutations in genes that encode cardiac ion channels. Nearly 25% of patients remain without a genetic diagnosis, and genes that encode cardiac channel regulatory proteins represent attractive candidates. Voltage-gated sodium channels have a pore-forming alpha-subunit associated with 1 or more auxiliary beta-subunits. Four different beta-subunits have been described. All are detectable in cardiac tissue, but none have yet been linked to any heritable arrhythmia syndrome. METHODS AND RESULTS: We present a case of a 21-month-old Mexican-mestizo female with intermittent 2:1 atrioventricular block and a corrected QT interval of 712 ms. Comprehensive open reading frame/splice mutational analysis of the 9 established LQTS-susceptibility genes proved negative, and complete mutational analysis of the 4 Na(vbeta)-subunits revealed a L179F (C535T) missense mutation in SCN4B that cosegregated properly throughout a 3-generation pedigree and was absent in 800 reference alleles. After this discovery, SCN4B was analyzed in 262 genotype-negative LQTS patients (96% white), but no further mutations were found. L179F was engineered by site-directed mutagenesis and heterologously expressed in HEK293 cells that contained the stably expressed SCN5A-encoded sodium channel alpha-subunit (hNa(V)1.5). Compared with the wild-type, L179F-beta4 caused an 8-fold (compared with SCN5A alone) and 3-fold (compared with SCN5A + WT-beta4) increase in late sodium current consistent with the molecular/electrophysiological phenotype previously shown for LQTS-associated mutations. CONCLUSIONS: We provide the seminal report of SCN4B-encoded Na(vbeta)4 as a novel LQT3-susceptibility gene.

• The ATP-binding cassette transporter A1 R230C variant affects HDL cholesterol levels and BMI in the Mexican population: association with obesity and obesity-related comorbidities.

  Authors: M Teresa Villarreal-Molina, Carlos A Aguilar-Salinas, Maricela Rodríguez-Cruz, Daniela Riaño, Marisela Villalobos-Comparan, Ramon Coral-Vazquez, Marta Menjivar, Petra Yescas-Gomez, Mina Königsoerg-Fainstein, Sandra Romero-Hidalgo, M Teresa Tusie-Luna, Samuel Canizales-Quinteros

  Diabetes. 08/2007; 56(7):1881-7.

  Although ATP-binding cassette transporter A1 (ABCA1) is well known for its role in cholesterol efflux and HDL formation, it is expressed in various tissues, where it may have different functions.Although ATP-binding cassette transporter A1 (ABCA1) is well known for its role in cholesterol efflux and HDL formation, it is expressed in various tissues, where it may have different functions. Because hypoalphalipoproteinemia is highly prevalent in Mexico, we screened the ABCA1 coding sequence in Mexican individuals with low and high HDL cholesterol levels to seek functional variants. A highly frequent nonsynonymous variant (R230C) was identified in low-HDL cholesterol but not in high-HDL cholesterol individuals (P = 0.00006). We thus assessed its frequency in the Mexican-Mestizo general population, seeking possible associations with several metabolic traits. R230C was screened in 429 Mexican Mestizos using Taqman assays, and it was found in 20.1% of these individuals. The variant was significantly associated not only with decreased HDL cholesterol and apolipoprotein A-I levels but also with obesity (odds ratio 2.527, P = 0.005), the metabolic syndrome (1.893, P = 0.0007), and type 2 diabetes (4.527, P = 0.003). All of these associations remained significant after adjusting for admixture (P = 0.011, P = 0.001, and P = 0.006, respectively). This is the first study reporting the association of an ABCA1 variant with obesity and obesity-related comorbidities as being epidemiologically relevant in the Mexican population.

• A genomewide admixture map for Latino populations.

  Authors: Alkes L Price, Nick Patterson, Fuli Yu, David R Cox, Alicja Waliszewska, Gavin J McDonald, Arti Tandon, Christine Schirmer, Julie Neubauer, Gabriel Bedoya [......] Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros, Marta Menjivar, William Klitz, Brian Henderson, Christopher A Haiman, Cheryl Winkler, Teresa Tusie-Luna, Andres Ruiz-Linares, David Reich

  American journal of human genetics. 07/2007; 80(6):1024-36.

  Admixture mapping is an economical and powerful approach for localizing disease genes in populations of recently mixed ancestry and has proven successful in African Americans. The method holds equalAdmixture mapping is an economical and powerful approach for localizing disease genes in populations of recently mixed ancestry and has proven successful in African Americans. The method holds equal promise for Latinos, who typically inherit a mix of European, Native American, and African ancestry. However, admixture mapping in Latinos has not been practical because of the lack of a map of ancestry-informative markers validated in Native American and other populations. To address this, we screened multiple databases, containing millions of markers, to identify 4,186 markers that were putatively informative for determining the ancestry of chromosomal segments in Latino populations. We experimentally validated each of these markers in at least 232 new Latino, European, Native American, and African samples, and we selected a subset of 1,649 markers to form an admixture map. An advantage of our strategy is that we focused our map on markers distinguishing Native American from other ancestries and restricted it to markers with very similar frequencies in Europeans and Africans, which decreased the number of markers needed and minimized the possibility of false disease associations. We evaluated the effectiveness of our map for localizing disease genes in four Latino populations from both North and South America.

• Analysis of C-850T and G-308A polymorphisms of the tumor necrosis factor-alpha gene in Maya-Mestizo women with preeclampsia.

  Authors: Thelma Canto-Cetina, Samuel Canizales-Quinteros, Elsa De La Chesnaye, Ramón Coral-Vázquez, Juan Pablo Méndez, Patricia Canto

  Hypertension in pregnancy : official journal of the International Society for the Study of Hypertension in Pregnancy. 02/2007; 26(3):283-91.

  OBJECTIVE: To determine whether polymorphisms in the TNF-alpha promoter gene are associated with preeclampsia. METHODS: 105 women with preeclampsia and 200 controls were genotyped for the G-308A andOBJECTIVE: To determine whether polymorphisms in the TNF-alpha promoter gene are associated with preeclampsia. METHODS: 105 women with preeclampsia and 200 controls were genotyped for the G-308A and C-850T polymorphisms by RFLP. Differences in allele, genotype, and haplotype frequencies between groups were assessed. RESULTS: The genotypic and allelic distribution of both polymorphisms was similar between groups. Moreover, the estimated overall pair of loci haplotype frequencies did not differ significantly. CONCLUSION: We did not find any association between these polymorphisms and the risk for preeclampsia. However, we found that both the genotypic and allelic distribution in our population differed from those reported in other populations.

• Founder effect for the Ala431Glu mutation of the presenilin 1 gene causing early-onset Alzheimer's disease in Mexican families.

  Authors: Petra Yescas, Adriana Huertas-Vazquez, María Teresa Villarreal-Molina, Astrid Rasmussen, María Teresa Tusié-Luna, Marisol López, Samuel Canizales-Quinteros, María Elisa Alonso

  Neurogenetics. 08/2006; 7(3):195-200.

  The etiology of Alzheimer's disease (AD) is complex. To date, molecular genetic studies in several families affected with AD have identified three genes associated with highly penetrant early-onsetThe etiology of Alzheimer's disease (AD) is complex. To date, molecular genetic studies in several families affected with AD have identified three genes associated with highly penetrant early-onset AD: Presenilin 1 (PSEN1), Presenilin 2 (PSEN2) and beta-amyloid precursor protein (APP); and one gene (apolipoprotein E) associated with late-onset AD. Molecular analysis of the PSEN1 gene was performed by direct sequencing of genomic DNA. The possible founder effect was investigated analyzing two highly polymorphic microsatellite markers flanking the PSEN1 gene. Twelve unrelated Mexican families with early-onset AD were analyzed. The Ala431Glu mutation in exon 12 of PSEN1 was found in nine (75%) of these families, which segregated showing autosomal dominant inheritance. Because all families bearing the mutation are from the State of Jalisco (located in Western Mexico), a founder effect was hypothesized. Microsatellite haplotype analysis suggested a common ancestor in these nine kindreds. In conclusion, the Ala431Glu mutation is a prevalent cause of early-onset familial Alzheimer's disease in families from the State of Jalisco, Mexico. Genetic evidence supports that it is a founder mutation descending from a single common ancestor. These findings have important implications for prompt diagnosis and genetic counseling for Mexican patients with familial AD from Jalisco.

• Common hepatic nuclear factor-4alpha variants are associated with high serum lipid levels and the metabolic syndrome.

  Authors: Daphna Weissglas-Volkov, Adriana Huertas-Vazquez, Elina Suviolahti, Jenny Lee, Christopher Plaisier, Samuel Canizales-Quinteros, Teresa Tusie-Luna, Carlos Aguilar-Salinas, Marja-Riitta Taskinen, Päivi Pajukanta

  Diabetes. 08/2006; 55(7):1970-7.

  Hepatic nuclear factor-4alpha (HNF-4alpha), a transcription factor involved in the regulation of serum lipid and glucose levels, has recently been associated with type 2 diabetes. The HNF-4alpha geneHepatic nuclear factor-4alpha (HNF-4alpha), a transcription factor involved in the regulation of serum lipid and glucose levels, has recently been associated with type 2 diabetes. The HNF-4alpha gene (HNF4A) resides on chromosome 20q12-q13.1, which, in addition to type 2 diabetes, has also previously been linked to high triglycerides in Finnish familial combined hyperlipidemia (FCHL) families. FCHL, characterized by elevated levels of serum total cholesterol, triglycerides, or both, is a common dyslipidemia observed in up to 20% of patients with premature coronary heart disease. Considering the clear phenotypic overlap between type 2 diabetes and FCHL, both predisposing to high serum triglycerides and glucose intolerance, we tested this gene for association in dyslipidemic families originating from two distinct populations, Finnish and Mexican, and comprising 1,447 subjects. Our data show that common HNF4A variants and haplotypes are associated with elevated serum lipid levels and the metabolic syndrome (P = 0.008-0.04), as well as with elevated glucose parameters (P = 0.008-0.03), using family-based association analysis. Importantly, both Finnish and Mexican families shared two common lipid-associated HNF4A haplotypes (P = 0.005 for total cholesterol and 0.006 for triglycerides). In conclusion, we show for the first time that common HNF4A variants are associated with high serum lipid levels and the metabolic syndrome.