Contribution of common genetic variation to the risk of type 2 diabetes in the Mexican Mestizo population

Diabetes. 2012 Dec;61(12):3314-21. doi: 10.2337/db11-0550. Epub 2012 Aug 24.

Abstract

Several studies have identified nearly 40 different type 2 diabetes susceptibility loci, mainly in European populations, but few of them have been evaluated in the Mexican population. The aim of this study was to examine the extent to which 24 common genetic variants previously associated with type 2 diabetes are associated in Mexican Mestizos. Twenty-four single nucleotide polymorphisms (SNPs) in or near genes (KCNJ11, PPARG, TCF7L2, SLC30A8, HHEX, CDKN2A/2B, CDKAL1, IGF2BP2, ARHGEF11, JAZF1, CDC123/CAMK1D, FTO, TSPAN8/LGR5, KCNQ1, THADA, ADAMTS9, NOTCH2, NXPH1, RORA, UBQLNL, and RALGPS2) were genotyped in Mexican Mestizos. A case-control association study comprising 1,027 type 2 diabetic individuals and 990 control individuals was conducted. To account for population stratification, a panel of 104 ancestry-informative markers was analyzed. Association to type 2 diabetes was found for rs13266634 (SLC30A8), rs7923837 (HHEX), rs10811661 (CDKN2A/2B), rs4402960 (IGF2BP2), rs12779790 (CDC123/CAMK1D), and rs2237892 (KCNQ1). In addition, rs7754840 (CDKAL1) was associated in the nonobese type 2 diabetic subgroup, and for rs7903146 (TCF7L2), association was observed for early-onset type 2 diabetes. Lack of association for the rest of the variants may have resulted from insufficient power to detect smaller allele effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinase Type 1 / genetics
  • Cation Transport Proteins / genetics
  • Cyclin-Dependent Kinase 5 / genetics
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study
  • Genotype
  • Homeodomain Proteins / genetics
  • Humans
  • KCNQ1 Potassium Channel / genetics
  • Male
  • Mexico
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • RNA-Binding Proteins / genetics
  • Transcription Factor 7-Like 2 Protein / genetics
  • Transcription Factors / genetics
  • Zinc Transporter 8
  • tRNA Methyltransferases

Substances

  • CDKN2B protein, human
  • Cation Transport Proteins
  • Cyclin-Dependent Kinase Inhibitor p15
  • HHEX protein, human
  • Homeodomain Proteins
  • IGF2BP2 protein, human
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • RNA-Binding Proteins
  • SLC30A8 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • Zinc Transporter 8
  • tRNA Methyltransferases
  • Cyclin-Dependent Kinase 5
  • CAMK1D protein, human
  • Calcium-Calmodulin-Dependent Protein Kinase Type 1
  • CDKAL1 protein, human