María Teresa Tusié-Luna

Publications of María Teresa Tusié-Luna

• [Familial homozygous hypercholesterolemia due to the c2271delT mutation in the LDL receptor gene, detected exclusively in mexicans].

  Authors: Lizbeth Martínez, María Luisa Ordóñez Sánchez, Rosario Letona, Verónica Olvera Sumano, Mariano Miguel Guerra, María Teresa Tusié-Luna, Carlos Alberto Aguilar-Salinas

  Gaceta médica de México. 09/2011; 147(5):394-8.

  We present the case of an 18-years old women with homozygous familial hypercholesterolemia in which a LDL receptor mutation (c2271delT) was found. This mutation has been informed only in Mexicans.We present the case of an 18-years old women with homozygous familial hypercholesterolemia in which a LDL receptor mutation (c2271delT) was found. This mutation has been informed only in Mexicans. The patient was born in Oaxaca, Mexico. She has atypical location of tendinous and tuberous xanthomata, coronary atherosclerosis and multiple valve involvement. The response to ezetimibe/high dose statin therapy was poor. This case is an example of the occurrence of homozygous forms of familial hypercholesterolemia in genetically isolated populations of Mexico.

• 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.

• [Fifty years studying hiperlipidemias: the case of familial combined hyperlipidemia].

  Authors: Carlos Aguilar-Salinas, Rita Gómez-Díaz, María Teresa Tusié-Luna

  Investigación clínica. 06/2010; 51(2):145-58.

  Familial combined hyperlipidemia (FCHL) is the most frequent primary dyslipidemia. Its manifestations include hypercholesterolemia, hypertriglyceridemia or the combination of both abnormalities. InFamilial combined hyperlipidemia (FCHL) is the most frequent primary dyslipidemia. Its manifestations include hypercholesterolemia, hypertriglyceridemia or the combination of both abnormalities. In spite of its high frequency, the proper diagnosis is rarely done. For this purpose, the measurement of a lipid profile is required in at least three first-degree relatives. A critical review of the current literature in this field is presented in this paper. Prospective studies have confirmed the atherogenicity of the disease. It is possible to identify the FCHL causal genes with the current methodology because it is an oligogenic disease. Based on the use of new technologies, several loci that regulate apolipoprotein B concentrations have been identified. In addition it was demostrated that variations of the activity or the expression of various nuclear factors (USF1, TCF7L2, HNF4alfa) have a major role in the pathophysiology of FCHL. These nuclear factors regulate the expression of multiple genes involved in the metabolism of lipids or carbohydrates.

• La obesidad y el síndrome metabólico como problema de salud pública. Una reflexión. Segunda parte

  Authors: Eduardo García-García, Manuel De la Llata-Romero, Kaufer-Horwitz Martha, María Teresa Tusié-Luna, Raúl Calzada-León, Verónica Vázquez Velásquez, Simón Barquera-Cervera, Alejandro de Jesús Caballero-Romo, Orozco Lorena, David Velázquez-Fernández, Martín Rosas Peralta, José Armando Barriguete Meléndez, Rogelio Zacarías-Castillo R, Julio Sotelo Morales

  Salud Mental. 01/2009;

• 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.

• Von Hippel-Lindau disease germline mutations in Mexican patients with cerebellar hemangioblastoma.

  Authors: Astrid Rasmussen, Sonia Nava-Salazar, Petra Yescas, Elisa Alonso, Rogelio Revuelta, Iván Ortiz, Samuel Canizales-Quinteros, María Teresa Tusié-Luna, Marisol López-López

  Journal of neurosurgery. 04/2006; 104(3):389-94.

  OBJECT: Central nervous system (CNS) hemangioblastomas are benign vascular tumors arising either sporadically or as a manifestation of von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome.OBJECT: Central nervous system (CNS) hemangioblastomas are benign vascular tumors arising either sporadically or as a manifestation of von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome. The authors studied a series of patients with CNS hemangioblastomas and their families to identify germline mutations in the VHL tumor suppressor gene and to establish a predictive testing and screening protocol. METHODS: Patients admitted between 2002 and 2004 to the Instituto Nacional de Neurología y Neurocirugía for hemangioblastoma were prospectively enrolled, together with their at-risk family members. The authors performed the molecular analysis of the VHL gene by using polymerase chain reaction and direct genetic sequencing. All asymptomatic mutation carriers underwent genetic counseling and tumor surveillance. Ninety-eight individuals were tested for VHL mutations--23 symptomatic and 75 asymptomatic individuals belonging to 16 families. Seven of the families had definite clinical criteria of VHL disease, five had sporadic hemangioblastoma, and four had CNS hemangioblastoma combined with minor visceral signs. Molecular genetic testing identified five germline mutations in six of the definite VHL families (sensitivity 85%), but none in the possible VHL and sporadic hemangioblastoma cases; four of these mutations had been previously described and one is a novel mutation present in two unrelated families. After patients carrying the mutation were identified, they underwent clinical screening and asymptomatic VHL-related lesions were identified in 43%. CONCLUSIONS: Genetic testing for mutations in the VHL gene is crucial in patients with CNS hemangioblastoma. The prompt identification of patients carrying the genetic mutation allows for a multidisciplinary screening protocol to decrease morbidity and mortality rates in these patients, while avoiding costly and invasive procedures for noncarriers.

• GENEHUNTER versus SimWalk2 in the context of an extended kindred and a qualitative trait locus.

  Authors: Sandra Romero-Hidalgo, Eliane R Rodrigues, Eduardo Gutiérrez-Peña, Laura Riba, María Teresa Tusié-Luna

  Genetica. 04/2005; 123(3):235-44.

  GENEHUNTER and SimWalk2 are among the most commonly used software for parametric multipoint linkage analysis. In the context of extended kindred analysis, GENEHUNTER has a limitation in terms of theGENEHUNTER and SimWalk2 are among the most commonly used software for parametric multipoint linkage analysis. In the context of extended kindred analysis, GENEHUNTER has a limitation in terms of the number of individuals it can handle. One solution is to manually split the kindred into smaller pedigrees. SimWalk2 can handle a much larger number of individuals. However, its major drawback is the time it takes to process the data when compared to GENEHUNTER. Aside from the limitations of each program, when studying extended kindreds researchers are typically confronted with missing data. In this work we used simulated genotype data based on the structure of a real extended pedigree in order to compare the results obtained through GENEHUNTER and SimWalk2, evaluate the effect of discarding individuals and splitting the kindred on the logarithm of odds (lod) score, and to assess how missing data affect the performance of each program. Our results show that (1) for pedigrees of a moderate size, GENEHUNTER and SimWalk2 produce nearly the same results; (2) when using GENEHUNTER, either splitting the kindred into smaller sub-pedigrees or discarding individuals has an adverse effect when compared to the results obtained when using SimWalk2 with the whole pedigree; and (3) the performance of both programs is qualitatively similar in the missing data scenario. These conclusions are based on the sample distributions of the lod score values and of the estimates of the recombination fraction.

• 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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• [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.

• [Obesity and metabolic syndrome. A challenge for the Mexican Institutes of Health]

  Authors: Eduardo García-García, Manuel De la Llata-Romero, Martha Kaufer Horwitz, María Teresa Tusié-Luna, Raúl Calzada-León, Verónica Vázquez-Velázquez, Simón Barquera-Cervera, Alejandro de Jesús Caballero-Romo, Lorena Orozco, David Velázquez-Fernández, Martín Rosas Peralta, Armando Barriguete-Meléndez, Rogelio Zacarías-Castillo, Carlos Ortega-González, Julio Sotelo Morales

  Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición. 61(4):337-46.

  Numerous efforts for the development of basic and clinical research in obesity are being made by the National Institutes of Health and Federal Reference Hospitals in Mexico. However, greaterNumerous efforts for the development of basic and clinical research in obesity are being made by the National Institutes of Health and Federal Reference Hospitals in Mexico. However, greater interaction among researchers and stronger efforts towards the dissemination of the results are needed. The document outlines the general ideas and proposals of the Academic Group for the Study, Prevention and Treatment of Obesity and Metabolic Syndrome of the Coordinating Committee of the National Institutes of Health and High Specialty Hospitals (CCINSHAE). This is the first step in developing common objectives, with the aim of understanding the effect of these entities in public health and to establish guidelines to limit and eventually overcome them. We discuss the appropriateness of analyzing obesity and the metabolic syndrome together, and the current management of these entities at the National Institutes of Health in Mexico. The problems that arise in clinical practice lead to the need to generate a new model of medical care, including a new health worker and a new patient. It is imperative to establish permanent lines of communication and education with health personnel and with patients. The group proposes an integrated approach for research in these areas. Finally, a master plan that links the National Institutes of Health, particularly in the areas of research and programs within the institutions, is required as a first step in seeking answers useful in solving the problem. The second step would be linking the first and second levels of care through concrete actions needed to limit and reduce obesity and metabolic syndrome in the population.

• La obesidad y el síndrome metabólico como problema de salud pública: una reflexión

  Authors: Eduardo García-García, Manuel De la Llata-Romero, Martha Kaufer Horwitz, María Teresa Tusié-Luna, Raúl Calzada-León, Verónica Vázquez-Velázquez, Simón Barquera-Cervera, Alejandro Caballero Romo, Lorena Orozco, David Velásquez Fernández, Martín Rosas Peralta, Jorge Armando Barriguete-Meléndez, Rogelio Zacarías-Castillo, Julio Sotelo Morales

  Salud pública de México, ISSN 0036-3634, Vol. 50, Nº. 6, 2008, pags. 530-547.

• Familial hypobetalipoproteinemia in a hospital survey: genetics, metabolism and non-alcoholic fatty liver disease.

  Authors: Carlos Gutiérrez-Cirlos, María Luisa Ordóñez-Sánchez, María Teresa Tusié-Luna, Bruce W Patterson, Gustav Schonfeld, Carlos A Aguilar-Salinas

  Annals of hepatology : official journal of the Mexican Association of Hepatology. 10(2):155-64.

  Familial hypobetalipoproteinemia (FHBL) is an autosomal dominant disease characterized by abnormally low levels of apolipoprotein-B (apoB) containing lipoproteins. FHBL is caused by APOB, PCSK9 orFamilial hypobetalipoproteinemia (FHBL) is an autosomal dominant disease characterized by abnormally low levels of apolipoprotein-B (apoB) containing lipoproteins. FHBL is caused by APOB, PCSK9 or ANGPTL3 mutations or is associated with loci located in chromosomes 10 and 3p21. However, other genes should be involved. This study describes the kinetic parameters of the apoB containing lipoproteins and sequence abnormalities of the APOB and PCSK9 genes of FHBL patients identified in a large hospital based survey. Cases with primary or secondary causes of hypobetalipoproteinemia were identified. ApoB kinetics were measured in cases with primary forms in whom truncated forms of apoB were not present in VLDL (n = 4). A primed constant infusion of [(13)C] leucine was administered, VLDL and LDL apoB production and catabolic rates measured by a multicompartmental model and compared to normolipemic controls. In addition, these subjects had an abdominal ultrasound and direct sequencing was carried out for the PCSK9 and apoB genes. Three individuals had normal apoB production with increased catabolic rate; the remaining had reduced synthetic and catabolic rates. Various polymorphisms, some of them previously unreported (*), in the PCSK9 gene (R46L, A53V, I474V, D480N*, E498K*) and in the apoB gene (N441D*, Y1395C, P2712L, D2285E*, I2286V, T3540S*, T3799M*) were found in the FHBL patients. We found hepatic ultrasound changes of hepatic steatosis in only one of the four probands. FHBL without truncated apoB is a heterogeneous disease from a metabolic and a genetic perspective. Hypobetalipoproteinemia is a risk factor but not an obligate cause of steatosis.

• Genes and type 2 diabetes mellitus.

  Authors: María Teresa Tusié-Luna

  Archives of medical research. 36(3):210-22.

  Type 2 diabetes (T2DM) comprises a group of entities with different genetic causes. In most patients, T2DM results from alterations of various genes, each having a partial and additive effect. TheType 2 diabetes (T2DM) comprises a group of entities with different genetic causes. In most patients, T2DM results from alterations of various genes, each having a partial and additive effect. The inheritance pattern is thus complex, and environmental factors play an important role in favoring or delaying the expression of the disease. The identification of susceptibility genes and genetic variants requires different methodological approaches. Here we address some of the most important strategies and findings on the genomic basis of T2DM, as well as evidence of genetic heterogeneity among populations. The identification of the underlying genetic causes of T2DM and other related traits such as obesity and hypertension will lead to the development of new therapeutic targets likely to impact the way we treat these diseases. Survival and quality of life for T2DM patients is expected to eventually increase, significantly lessening the socioeconomic burden of the disease.

• [In Process Citation]

  Authors: Eduardo García-García, Manuel De la Llata-Romero, Martha Kaufer Horwitz, María Teresa Tusié-Luna, Raúl Calzada-León, Verónica Vázquez-Velázquez, Simón Barquera-Cervera, Alejandro de Jesús Caballero-Romo, Lorena Orozco, David Velásquez Fernández, Martín Rosas Peralta, Armando Barriguete-Meléndez, Rogelio Zacarías-Castillo, Julio Sotelo Morales

  Salud pública de México. 50(6):530-47.

• [Succesful collaborations between three Mexican institutions for research on dislipidemias, obesity and diabetes]

  Authors: Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros, Rosalba Rojas-Martínez, Eduardo García-García, Gustavo Olaiz-Fernández, Francisco J Gómez-Pérez, María Teresa Tusié-Luna

  Gaceta médica de México. 143(5):355-64.

  OBJECTIVE: To describe the contributions ofthree Mexican institutions (Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Universidad Nacional Autónoma de México and the Centro deOBJECTIVE: To describe the contributions ofthree Mexican institutions (Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Universidad Nacional Autónoma de México and the Centro de Encuestas Nacionales de Salud of the Instituto Nacional de Salud Pública) in the study, of chronic degenerative disorders. RESULTS: The most relevant group contributions include: the identification of a risk allele for metabolic syndrome and diabetes, specific for the Mexican population (the R230C variant of the ABC-A1 transporter); the design and validation of a population-based definition of metabolic syndrome which is useful to predict the risk of incident diabetes; the description of the molecular epidemiology of familial hypercholesterolemia in Mexico and the identification of several loci associated with familial combined hyperlipidemia. In addition, members of these institutions have participated in the description of the epidemiology of diabetes, metabolic syndrome and lipid abnormalities. CONCLUSIONS: The complementary approach of these research groups has facilitated successful collaborations. Our results will be useful for the future development of diagnostic tests and preventive programs.