Salvador Ramírez-Jiménez

Publications of Salvador Ramírez-Jiménez

• 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.

• Galanin Preproprotein Is Associated With Elevated Plasma Triglycerides.

  Authors: Christopher L Plaisier, Mira Kyttälä, Daphna Weissglas-Volkov, Janet S Sinsheimer, Adriana Huertas-Vazquez, Laura Riba, Salvador Ramírez-Jiménez, Tjerk W A de Bruin, Teresa Tusié-Luna, Bradley E Aouizerat [......] Mary J Malloy, John P Kane, Ivette Cruz-Bautista, Miguel F Herrera, Carlos Aguilar-Salinas, Johanna Kuusisto, Markku Laakso, Marja-Riitta Taskinen, Carla J H van der Kallen, Päivi Pajukanta

  Arteriosclerosis, thrombosis, and vascular biology. 12/2008;

  OBJECTIVE: There is increasing physiological evidence in rodents connecting the neuropeptide galanin to triglyceride (TG) levels. We hypothesized that variation in the galanin preproprotein (GAL)OBJECTIVE: There is increasing physiological evidence in rodents connecting the neuropeptide galanin to triglyceride (TG) levels. We hypothesized that variation in the galanin preproprotein (GAL) gene may contribute to hypertriglyceridemia (HTG) in humans. METHODS AND RESULTS: We investigated GAL as a TG candidate gene by genotyping 4 tagSNPs in Dutch, Finnish, and Mexican familial combined hyperlipidemia (FCHL) families as well as in white combined hyperlipidemia cases/controls (n=2471). The common allele of rs2187331, residing in the promoter region of GAL, was significantly associated with HTG (probability value=0.00038). In an unascertained population sample of 4463 Finnish males, the rare allele of rs2187331 was associated with higher TGs (probability value=0.0028 to 0.00016). We also observed an allele specific difference with rs2187331 in reporter gene expression and nuclear factor binding in vitro. Furthermore, we detected differential expression of many key lipid genes in adipose tissue based on rs2187331 genotypes. CONCLUSIONS: The SNP rs2187331 is associated with HTG in FCHL and white combined hyperlipidemia cases/controls and influences TG levels in the population. Further studies are warranted to elucidate the allelic difference observed between FCHL and the general population. Functional evidence shows that rs2187331 has an allele specific cis-regulatory function and influences the expression of lipid related genes in adipose.

• Mutations in MODY genes are not common cause of early-onset type 2 diabetes in Mexican families.

  Authors: Aarón Domínguez-López, Angel Miliar-García, Yayoi X Segura-Kato, Laura Riba, Riba Esparza-López, Salvador Ramírez-Jiménez, Maribel Rodríguez-Torres, Samuel Canizales-Quinteros, Siraam Cabrera-Vásquez, Verónica Fragoso-Ontiveros, Carlos A Aguilar-Salinas, Nelly Altamirano-Bustamante, Raúl Calzada-León, Carlos Robles-Valdés, Luz E Bravo-Ríos, Maria Teresa Tusié-Luna

  JOP : Journal of the pancreas. 06/2005; 6(3):238-45.

  CONTEXT: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset and a primary insulin secretionCONTEXT: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset and a primary insulin secretion defect. Certain MODY gene sequence variants may be involved in polygenic forms of type 2 diabetes. OBJECTIVE: We assessed the contribution of MODY genes to the etiology of type 2 early-onset diabetes in 23 Mexican families, including five with apparently autosomal dominant inheritance. PATIENTS: Twenty-three unrelated Mexican families with early-onset type 2 diabetes previously screened for the presence of glucokinase mutations, were studied. DESIGN: We screened MODY genes for sequence variants by PCR-SSCP analysis and automated sequencing. We performed a functional analysis of the HNF-1alpha P379H recombinant protein in vitro in both HeLa and RINm5f beta-cell lines. MAIN OUTCOME MEASURES: MODY gene mutation screening and P379H mutant protein transactivation assay. RESULTS: No mutations were detected in the HNF-4alpha, IPF-1, NEUROD1 or HNF-1beta genes in any of the families studied. A new mutation (P379H) of the HNF-1alpha gene was identified in one MODY family. RINm5f and HeLa cell transfection assays revealed decreased transactivation activity of the mutant protein on the human insulin promoter. CONCLUSIONS: All known MODY genes were screened for abnormalities in this cohort of early-onset diabetes families which included 5 MODY pedigrees. We identified a new HNF-1alpha MODY mutation (P379H) and demonstrated that it reduces the transactivation potential of the mutant protein on the human insulin promoter. No other mutation was identified in this cohort indicating that abnormalities in MODY genes are generally not a common cause of early-onset diabetes and this includes MODY families in Mexico.

• Association of the calpain-10 gene with type 2 diabetes mellitus in a Mexican population.

  Authors: Laura Del Bosque-Plata, Carlos A Aguilar-Salinas, María Teresa Tusié-Luna, Salvador Ramírez-Jiménez, Maribel Rodríguez-Torres, Moisés Aurón-Gómez, Erika Ramírez, María Luisa Velasco-Pérez, Alfredo Ramírez-Silva, Francisco Gómez-Pérez, Craig L Hanis, Takafumi Tsuchiya, Issei Yoshiuchi, Nancy J Cox, Graeme I Bell

  Molecular genetics and metabolism. 03/2004; 81(2):122-6.

  Variation in the calpain-10 gene (CAPN10) has been associated with risk of type 2 diabetes in the Mexican American population of Starr County, Texas. We typed five polymorphisms in the calpain-10Variation in the calpain-10 gene (CAPN10) has been associated with risk of type 2 diabetes in the Mexican American population of Starr County, Texas. We typed five polymorphisms in the calpain-10 gene (SNP-43, -43, -63, and -110 and Indel-19) to test for association with type 2 diabetes in 248 individuals representative of the mestizo population of Mexico City and Orizaba, Mexico including 134 patients with type 2 diabetes and 114 subjects with normal fasting blood glucose levels. We found a significant difference in SNP-44 allele and genotype frequencies between type 2 diabetic and non-diabetic subjects. The rare allele at SNP-44 was associated with increased risk of type 2 diabetes (odds ratio (OR)=2.72, 95% confidence interval (CI)=1.16-6.35, P=0.017). SNP-110, which is in perfect linkage disequilibrium with SNP-44, was also associated with type 2 diabetes. The SNP-43, Indel-19, and SNP-63 haplogenotype 112/121 associated with significantly increased risk (OR=2.16, 95% CI=1.31-3.57) of type 2 diabetes in Mexican Americans was not associated with significantly increased in risk in Mexicans (OR=1.15, 95% CI=0.57-2.34). The results suggest that variation in CAPN10 affects risk of type 2 diabetes in the mestizo population of central Mexico (Mexico City and Orizaba) and in Mexican Americans (Starr County, Texas).

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• Steroid 21-hydroxylase (P450c21) naturally occurring mutants I172N, V281L and I236n/V237E/M239K exert a dominant negative effect on enzymatic activity when co-expressed with the wild-type protein.

  Authors: Xóchitl Félix-López, Laura Riba, M Luisa Ordóñez-Sánchez, Salvador Ramírez-Jiménez, José Luis Ventura-Gallegos, Alejandro Zentella-Dehesa, M Teresa Tusié-Luna

  Journal of pediatric endocrinology & metabolism : JPEM. 10/2003; 16(7):1017-24.

  Steroid 21-hydroxylase deficiency is the major cause of congenital adrenal hyperplasia, an autosomic recessive disorder that affects the synthesis of aldosterone and cortisol. The disease presents aSteroid 21-hydroxylase deficiency is the major cause of congenital adrenal hyperplasia, an autosomic recessive disorder that affects the synthesis of aldosterone and cortisol. The disease presents a wide spectrum of clinical phenotypes as a result of the combination of different mutant alleles. Due to the adrenal-specific expression of the enzyme, the study of the functional effect of different mutations is only possible through in vitro expression studies. Determination of the functional effect of independent mutations does not always result in clear phenotype-genotype correlations, particularly in those patients with different mutations in the two alleles (compound heterozygotes). In this study we show that co-expression of the mutant proteins I172N, V281L or I236N/V237E/M239K with the wild-type enzyme resulted in an apparent dominant negative effect on the enzymatic activity of the latter, while co-expression with the mutant enzyme R356W does not show this effect.

• Locus on chromosome 6p linked to elevated HDL cholesterol serum levels and to protection against premature atherosclerosis in a kindred with familial hypercholesterolemia.

  Authors: Samuel Canizales-Quinteros, Carlos A Aguilar-Salinas, Eduardo Reyes-Rodríguez, Laura Riba, Maribel Rodríguez-Torres, Salvador Ramírez-Jiménez, Adriana Huertas-Vázquez, Verónica Fragoso-Ontiveros, Alejandro Zentella-Dehesa, José L Ventura-Gallegos, Gerardo Vega-Hernández, Angelina López-Estrada, Moisés Aurón-Gómez, Francisco Gómez-Pérez, Juan Rull, Nancy J Cox, Graeme I Bell, Maria Teresa Tusié-Luna

  Circulation research. 04/2003; 92(5):569-76.

  Heterozygous familial hypercholesterolemia (FH) is a highly atherogenic genetic disorder leading to premature coronary heart disease (CHD), usually before 60 years of age. We studied an extendedHeterozygous familial hypercholesterolemia (FH) is a highly atherogenic genetic disorder leading to premature coronary heart disease (CHD), usually before 60 years of age. We studied an extended multigenerational kindred with FH linked to chromosome 1p32 in which atherosclerotic complications were either delayed or prevented in individuals with elevated HDL cholesterol (HDL-C) levels or hyperalphalipoproteinemia (HA). Premature CHD was observed in FH individuals without HA. The study of this family established that the HA trait in the family also followed an autosomal dominant mode of inheritance with a pattern of segregation independent from FH. We identified a locus on chromosome 6 linked to elevated HDL-C levels (HA) in this family. Haplotype analysis refined the localization to a 7.32-cM interval (73 to 80 cM from pter) flanked by markers D6S1280 and D6S1275. Parametric 2-point and multipoint analyses yielded maximum LOD scores of 3.05 and 3.17, respectively. This finding was confirmed with a nonparametric multipoint score of 3.78 (P=0.0009). We propose that this locus, linked to elevated HDL-C levels, confers protection against premature CHD within an FH context.

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• [Identifying different susceptibility loci associated with early onset diabetes and cardiovascular disease in Mexican families]

  Authors: Samuel Canizales-Quinteros, Adriana Huertas-Vázquez, Laura Riba-Ramírez, Adriana Monroy-Guzmán, Aarón Domínguez-López, Sandra Romero-Hidalgo, Carlos Aguilar-Salinas, Maribel Rodríguez-Torres, Salvador Ramírez-Jiménez, María Teresa Tusié-Luna

  Gaceta médica de México. 141(2):115-22.

  Coronary artery disease and diabetes mellitus are among the primary mortality and morbidity causes in Mexico. Genetic factors play a fundamental role in the development of these entities. In the pastCoronary artery disease and diabetes mellitus are among the primary mortality and morbidity causes in Mexico. Genetic factors play a fundamental role in the development of these entities. In the past few years due to the recognition and study of families with monogenic forms of diabetes and dislipidemias associated with development of atherosclerosis, several genes and loci have been associated with these conditions through genetic linkage studies. These studies have provided evidence of the genetic heterogeneity that exists and the type of genes involved in different ethnic groups. The study of Mexican families with early-onset diabetes and combined familial hyperlipidemia showed the participation of different genetic loci associated with these conditions in the Mexican population. These findings show the value of gene mapping strategies in the identification of the genetic component in these entities in our population.