S Canizales-Quinteros

Publications of S Canizales-Quinteros

• High frequency of T130I mutation of HNF4A gene in Mexican patients with early-onset type 2 diabetes.

  Authors: M Menjívar, M A Granados-Silvestre, I Montúfar-Robles, M Herrera, M T Tusié-Luna, S Canizales-Quinteros, C A Aguilar-Salinas, M G Ortiz-López

  Clinical genetics. 03/2008; 73(2):185-7.

• TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia.

  Authors: A Huertas-Vazquez, C Plaisier, D. Weissglas-Volkov, J Sinsheimer, S Canizales-Quinteros, I Cruz-Bautista, E Nikkola, M Herrera-Hernandez, A Davila-Cervantes, T. Tusie-Luna, M R Taskinen, C Aguilar-Salinas, P Pajukanta

  Diabetologia. 02/2008; 51(1):62-9.

  AIMS/HYPOTHESIS: Common DNA variants of the transcription factor 7-like 2 gene (TCF7L2) are associated with type 2 diabetes. Familial combined hyperlipidaemia (FCHL) is characterised byAIMS/HYPOTHESIS: Common DNA variants of the transcription factor 7-like 2 gene (TCF7L2) are associated with type 2 diabetes. Familial combined hyperlipidaemia (FCHL) is characterised by hypertriacylglycerolaemia, hypercholesterolaemia, or both. Additionally, disturbances in glucose metabolism are commonly seen in FCHL. Therefore, we hypothesised that TCF7L2 may contribute to the genetic susceptibility for this common dyslipidaemia. METHODS: We investigated the effect of the TCF7L2 variants, rs7903146 and rs12255372, on FCHL and its component traits triacylglycerol (TG), total cholesterol (TC) and apolipoprotein B (ApoB) in 759 individuals from 55 Mexican families. As a replication sample, 719 individuals from 60 Finnish FCHL families were analysed. We also used quantitative RT-PCR to evaluate the transcript levels of TCF7L2 in 47 subcutaneous fat biopsies from unrelated Mexican FCHL and normolipidaemic participants. RESULTS: Significant evidence for association was observed for high TG for the T alleles of rs7903146 and rs12255372 (p = 0.005 and p = 0.01) in Mexican FCHL families. No evidence for association was observed for FCHL, TC, ApoB or glucose in Mexicans. When testing rs7903146 and rs12255372 for replication in Finnish FCHL families, these single nucleotide polymorphisms were associated with TG (p = 0.01 and p = 0.007). Furthermore, we observed statistically significant decreases in the mRNA levels (p = 0.0002) of TCF7L2 in FCHL- and TG-affected individuals. TCF7L2 expression was not altered by the SNP genotypes. CONCLUSIONS/INTERPRETATION: These data show that rs7903146 and rs12255372 are significantly associated with high TG in FCHL families from two different populations. In addition, significantly decreased expression of TCF7L2 was observed in TG- and FCHL-affected individuals.

• Association of PPARG2 Pro12Ala variant with larger body mass index in Mestizo and Amerindian populations of Mexico.

  Authors: S Canizales-Quinteros, C A Aguilar-Salinas, M G Ortiz-López, M Rodríguez-Cruz, M T Villarreal-Molina, R Coral-Vázquez, A Huertas-Vázquez, A Hernández-Caballero, M López-Alarcón, O R Brito Zurita, A Domínguez-Banda, L R Martinez-Sánchez, T Canto-de Cetina, G Vilchis-Dorantes, H Rosas-Vargas, M A Granados-Silvestre, A Medeiros-Domingo, M. Menjivar, M T Tusié-Luna

  Human biology; an international record of research. 02/2007; 79(1):111-9.

  Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, withPrevious studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, with controversial results. We have determined the Pro12Ala variant frequency in 370 nondiabetic Mexican Mestizo subjects and in five Mexican Amerindian groups and have investigated its possible association with lipid metabolism, insulin serum levels, and obesity in three of these populations. Two independent case-control studies were conducted in 239 nondiabetic individuals: 135 case subjects (BMI > or = 25 kg/m2) and 104 control subjects (BMI < 25 kg/m2). The PPARG2 Ala12 allele frequency was higher in most Amerindian populations (0.17 in Yaquis, 0.16 in Mazahuas, 0.16 in Mayans, and 0.20 in Triquis) than in Asians, African Americans, and Caucasians. The Pro12Ala and Ala12Ala (X12Ala) genotypes were significantly associated with greater BMI in Mexican Mestizos and in two Amerindian groups. X12Ala individuals had a higher risk of overweight or obesity than noncarriers in Mestizos (OR = 3.67; 95% CI, 1.42-9.48; p = 0.007) and in Yaquis plus Mazahuas (OR = 3.21; 95% CI, 1.27-8.11; p = 0.013). Our results provide further support of the association between the PPARG2 Ala12 allele and risk of overweight or obesity in Mestizos and two Amerindian populations from Mexico.

• HNF-1alpha G574S is a functional variant with decreased transactivation activity.

  Authors: K Navalón-García, L Mendoza-Alcantar, M E Díaz-Vargas, M A Martínez-Godínez, H Reyna-Garfias, C A Aguilar-Salinas, L Riba, S Canizales-Quinteros, T Villarreal-Molina, A González-Chávez, V Argueta-Villamar, M T Tusié-Luna, A Miliar-García

  Diabetic medicine : a journal of the British Diabetic Association. 01/2007; 23(12):1295-300.

  AIM: To assess the functional consequence of the hepatocyte nuclear factor 1alpha gene (HNF-1alpha) G574S variant previously proposed as a diabetes susceptibility allele, in a group of Mexican Type 2AIM: To assess the functional consequence of the hepatocyte nuclear factor 1alpha gene (HNF-1alpha) G574S variant previously proposed as a diabetes susceptibility allele, in a group of Mexican Type 2 diabetic patients with end-stage renal disease (ESRD). METHODS: The transcriptional activity of the HNF-1alpha G574S recombinant protein on the human insulin promoter was assessed by transfection assays in RINm5f and HepG2 cell lines. RESULTS: Two unrelated Mexican diabetic patients with no known African ancestry were found to carry the G574S variant. This substitution was not found among unrelated healthy control subjects. Whereas the G574S HNF-1alpha transcription activation of the human insulin promoter was 40% lower than that of the wild-type protein in RINm5f beta cells, no difference was found in a hepatic cell line (HepG2). CONCLUSIONS: G574S affects the transactivation potential of HNF-1alpha on the insulin promoter in pancreatic beta-cells. Although it has been difficult to prove its role in the development of diabetes in case-control association studies, this variant exhibits functional effects consistent with it being a potential diabetes susceptibility allele.

• Mutations in MODY Genes Are not Common Cause of Early-Onset Type 2 Diabetes in Mexican Families

  Authors: C Robles-Valdés, A Miliar-García, YX Segura-Kato, L Riba, J Esparza-López, S Ramírez-Jiménez, M Rodríguez-Torres, S Canizales-Quinteros, S Cabrera-Vásquez, V Fragoso-Ontiveros, CA Aguilar-Salinas, N Altamirano-Ustamante, R Calzada-León, LE Bravo-Ríos, MT Tusié-Luna

  JOP Journal of the Pancreas. 01/2005;

  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.

• Contribution of chromosome 1q21-q23 to familial combined hyperlipidemia in Mexican families.

  Authors: A Huertas-Vázquez, J P del Rincón, S Canizales-Quinteros, L Riba, G Vega-Hernández, S Ramírez-Jiménez, M Aurón-Gómez, F J Gómez-Pérez, C A Aguilar-Salinas, M T Tusié-Luna

  Annals of human genetics. 10/2004; 68(Pt 5):419-27.

  Familial combined hyperlipidemia (FCHL) is the most common familial dyslipidemia, with a prevalence of 1-2% in the general population. A major locus for FCHL has been mapped to chromosome 1q21-q23 inFamilial combined hyperlipidemia (FCHL) is the most common familial dyslipidemia, with a prevalence of 1-2% in the general population. A major locus for FCHL has been mapped to chromosome 1q21-q23 in Finnish, Chinese, German and US families. We studied seven extended Mexican families with 153 members, including 64 affected subjects. A total of 11 markers were genotyped, including D1S104 which has been linked to FCHL in other studies. Two point linkage analysis for the FCHL phenotype, and for the elevated triglyceride (TG) trait, allowing for heterogeneity, gave a maximum HLOD of 1.67 (alpha = 0.49) and 1.93 (alpha = 0.43) at D1S2768 (2.69 cM proximal to D1S104) respectively. Heterogeneity and non-parametric (NPL) multipoint analyses for the FCHL phenotype and the TG trait showed maximum HLODs of 1.27 (alpha = 0.46) and 1.64 (alpha = 0.38), and NPLs of 4.00 (P = 0.0001) and 3.68 (P = 0.0003) near D1S2768, respectively. In addition, analysis of four candidate genes putatively involved in the expression of FCHL showed no evidence of linkage for the LCAT gene or the APOA1/C3/A4/A5 gene cluster. However, we cannot exclude the participation of these genes, or the LIPC and LPL genes, as minor susceptibility loci in the expression of FCHL, or the TG or elevated total cholesterol (TC) traits in our families. In conclusion, our data confirm the involvement of a major susceptibility locus on chromosome 1q21-q23 in FCHL Mexican families, consistent with findings in other populations.

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• A genomewide admixture map for latino populations

  Authors: A.L. Price, N Patterson, F. Yu, D.R. Cox, A. Waliszewska, G.J. McDonald, A. Tandon, C. Schirmer, J. Neubauer, G Bedoya [......] C A Aguilar-Salinas, S Canizales-Quinteros, M. Menjivar, W Klitz, B. Henderson, C.A. Haiman, C Winkler, T. Tusie-Luna, A Ruiz-Linares, D Reich

  Price, A.L. and Patterson, N. and Yu, F. and Cox, D.R. and Waliszewska, A. and McDonald, G.J. and Tandon, A. and Schirmer, C. and Neubauer, J. and Bedoya, G. and Duque, C. and Villegas, A. and Bortolini, M.C. and Salzano, F.M. and Gallo, C. and Mazzotti, G. and Tello-Ruiz, M. and Riba, L. and Aguilar-Salinas, C.A. and Canizales-Quinteros, S. and Menjivar, M. and Klitz, W. and Henderson, B. and Haiman, C.A. and Winkler, C. and Tusie-Luna, T. and Ruiz-Linares, A. and Reich, D. (2007) A genomewide admixture map for latino populations. The American Journal of Human Genetics, 80 (6). pp. 1024-1036. ISSN 00029297.

  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.

• [Role of the allelic E4 variant of apolipoprotein E in lipid concentrations in a Mexican rural indigenous population predisposed to type 2 diabetes mellitus]

  Authors: S Canizales-Quinteros, M T Tusié-Luna

  Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición. 52(3):314-7.