Replication of recently described type 2 diabetes gene variants in a South Indian population

Replication of 13 genome-wide association (GWA)-validated risk variants for type 2 diabetes in Pakistani populations

“…Of the variants studied, 13 displayed nominally significant associations with the disease ( Table 1). Seven of these variants are in regions that have previously demonstrated association with type 2 diabetes in South Asian populations; PPARG, TCF7L2, FTO, CDKN2A/2B, HHEX/IDE, IGF2BP2 and SLC30A8 [12,14,15]. To our knowledge, however, this study is the first to report significant associations between the disease and variants in or near KCNQ1, JAZF1, IRS1, KLF14, CHCHD9 and DUSP9 in a sizeable sample of South Asians.…”

“…Despite this progress, studies investigating the genetic basis of the disease in South Asian populations are still relatively limited and, to date, only four have attempted to replicate any of the findings of recent GWA studies [12][13][14][15]. The largest of these studies, investigating two Indian Asian populations [14], demonstrated that several variants displayed greater effect sizes than those previously seen in European studies, a fact that the authors attributed to higher genotype penetrance in Indian populations.…”

Pharmacogenetics for T2DM and Anti-Diabetic Drugs

“…Reduced www.intechopen.com CDKAL1 expression or inhibitory function could lead to an impaired response to glucotoxicity. The association of CDKAL1 rs7756992 with T2DM was replicated in Japanese [43], Chinese [30] and Indians populations [44]. And variants in CDKAL1 were strongly associated with -cell function estimated by HOMA-(Homeostasis model assessment for cell function) [30].…”

Genetic etiology of type 2 diabetes mellitus: a review

“…We have furnished results of these Indian studies in Table 5, which suggest strong role of common variants of T2DM susceptible genes such as TCF7L2, [40,41,138,139,142] PPARG [64,139,142] and CAPN10 [57,58] and some rare variants of genes such as LPL [69], ENPP1 (PC-1) [75], FTO [94,139], IRS-2 [96], PGC-1γ [84,85] and IL-4 & ILRN1 [98].The replicative studies of GWAS also show strong association of KCNJ11, [142] IGF2BP2, [139,142] CDKAL1, [142] SLC30A8 [142], CDKN2A [142,144], HHEX [142,143], CDKN2A/B, [143] and BAZ1 [143]. Of all the genes studied so far, TCF7L2 variants studied so far in the Indian populations (including the migrant Indians from UK [47]) show most significant and consistent association with T2DM, except for rs7901695 and rs12235572 [138].…”

“…TNFRSF1B polymorphisms did not reveal significant findings, although (TCC)n polymorphism of FOXA2 showed a strong association with T2DM. Out of the 45 SNPs of the AHI1, BAZ1B, CDKAL1, EXT2, HHEX, IGF2BP2, LOC387761, LOC441171, MC4R, MLXIPL, SLC30A8, STK32C, PPARG, and WFS1 genes tested, only BAZ1, CDKALI, CDKALI 2A/B and HHEX showed significant association with T2DM[143] in the population of Chennai, southern India.…”