title: Association of Gly972Arg polymorphism of IRS1 gene with type 2 diabetes mellitus in lean participants of a national health survey in Mexico: a candidate gene study.
abstract: Type 2 diabetes mellitus (T2D) is a main public health problem in the Mexican population. It is characterized by insulin resistance in peripheral tissues and a relative deficiency in the pancreatic beta-cell functions. Diverse single nucleotide polymorphisms (SNPs) of the IRS1 gene have been associated with insulin resistance and T2D risk. The aim of this study was to identify the association between known IRS1 polymorphisms (Pro512Ala, Asn1137Asp, Gly972Arg, and Arg158Pro) in a sample of diabetic patients compared with healthy controls selected from Mexico's 2000 National Health Survey, both with normal body mass index (BMI). We identified 444 diabetes cases that were age matched with the same number of controls. Genotypic and allelic frequencies were evaluated, and conditional logistic regression was used to evaluate the association between the SNPs and diabetes risk. Of the 4 SNPs studied, only Gly972Arg showed significant differences between cases and controls, with allele frequency of 2.6% in controls as compared with 7.9% in cases. Subjects with at least 1 copy of the Gly972Arg polymorphism of the IRS1 gene showed a greater risk for diabetes, with a crude odds ratio of 3.26 (95% confidence interval, 2.00-5.33); after adjusting for BMI, age, family history of T2D, and sex, the odds ratio was 2.91 (95% confidence interval, 1.73-4.90). Our results suggest the participation of Gly972Arg polymorphism of IRS1 in the genetic susceptibility to TD2 in Mexican population. The restriction of including only participants with normal BMI might increase the power to detect genetic determinants of T2D.
authors.affiliation: Centro de Enfermedades Infecciosas, Instituto Nacional de Salud Pública, México. aburguete@correo.insp.mx
authors.forename: Ana I
authors.initials: AI
authors.lastname: Burguete-Garcia
authors.forename: Miguel
authors.initials: M
authors.lastname: Cruz-Lopez
authors.forename: Vicente
authors.initials: V
authors.lastname: Madrid-Marina
authors.forename: Ruy
authors.initials: R
authors.lastname: Lopez-Ridaura
authors.forename: Mauricio
authors.initials: M
authors.lastname: Hernández-Avila
authors.forename: Bernardo
authors.initials: B
authors.lastname: Cortina
authors.forename: Rosa E
authors.initials: RE
authors.lastname: Gómez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Velasco-Mondragón
mesh_terms: D000368:Aged; D001120:Arginine / Q000235:genetics*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005998:Glycine / Q000235:genetics*; D006306:Health Surveys; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D016015:Logistic Models; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D001120:Arginine; D005998:Glycine