Contribution of Common Genetic Variation to the Risk of Type 2 Diabetes in the Mexican Mestizo Population

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.

Design of an allele-specific PCR assay to genotype the rs12255372 SNP in a pilot study of association between common TCF7L2 polymorphisms and type 2 diabetes in Venezuelans

“…Similarly, this polymorphism was found associated with diabetes in several works carried out in admixed populations from other Latin American countries (9,(23)(24)(25)28,29,31,32). However, Barros and cols.…”

“…Moreover, among Latin American countries there are only reports on the association of TCF7L2 polymorphisms and T2DM from Colombia (23), Brazil (24)(25)(26)(27)(28) and Mexico (9,(29)(30)(31)(32). Latin American populations are characterized by high socioeconomic and genetic heterogeneity with varying degrees of ancestral population proportions from country to country, thus more studies are needed exploring the basis of T2DM susceptibility from these mixed populations.…”

Association Between KCNQ1 Gene Polymorphism and Type 2 Diabetes Mellitus: Evidence from Meta-analysis

“…The association of rs2237892 polymorphism and rising T2DM incident risk proved former study result [2,4,[7][8][9][11][12][13][14][15][16][17][21][22][23][24]27,[29][30][31]36,[39][40][41][42][43][44][45][46]. East Asian, Southeast Asian and other region`s subgroup analysis also show the association still stable（OR=1.…”

Antiretroviral therapy modifies the genetic effect of known type 2 diabetes-associated risk variants in HIV-infected women

“…As the associations between DM and the SNPs interrogated are generally similar across non-African populations [22–29], we combined self-reported White, Hispanic, Asian, Native American, and Other women as one group (‘non-African-Americans’). Analyses were run separately for non-African-Americans (49 DM cases, 329 non-cases) and African-Americans (49 DM cases, 542 non-cases).…”

“…In 2007, four genome-wide association studies (GWAS) identified multiple alleles associated with DM in predominately European populations [17–21]. Replication studies in independent European, Asian, and Mexican populations have confirmed several of these DM risk variants [22–29]. However, it appears that different signals are observed in African populations due to the greater degree of diversity in linkage disequilibrium (LD) patterns in populations of African descent [25, 30–32].…”