Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population

Abstract

Aims/hypothesis New genetic variants associated with susceptibility to type 2 diabetes mellitus have been discovered in recent genome-wide association (GWA) studies. The aim of the present study was to examine the association between these diabetogenic variants and gestational diabetes mellitus (GDM). Methods The study included 869 Korean women with GDM and 345 female and 287 male Korean non-diabetic controls. We genotyped the single nucleotide polymorphisms (SNPs) rs7756992 and rs7754840 in CDKAL1; rs564398, rs1333040, rs10757278 and rs10811661 in the CDKN2A−CDKN2B region; rs8050136 in FTO; rs1111875, rs5015480 and rs7923837 in HHEX; rs4402960 in IGF2BP2; and rs13266634 in SLC30A8. In addition, rs7903146 and rs12255372 in TCF7L2; rs5215 and rs5219 in KCNJ11; and rs3856806 and rs1801282 in PPARG were genotyped. The genotype frequencies in the GDM patients were compared with those in the non-diabetic controls. Results Compared with controls (men and women combined), GDM was associated with rs7756992 and rs7754840 (OR 1.55, 95% CI 1.34-1.79, p=4.17×10 −9 ) in CDKAL1; rs10811661 (OR 1.49, 95% CI 1.29-1.72, p=1.05×10 −7 ) in the CDKN2A−CDKN2B region; rs1111875 (OR 1.27, 95% CI 1.09-1.49, p=0.003), rs5015480, and rs7923837 in HHEX; rs4402960 (OR 1.18, 95% CI 1.01-1.38, p=0.03) in IGF2BP2; rs13266634 (OR 1.24, 95% CI 1.07-1.43, p=0.005) in SLC30A8; and rs7903146 (OR 1.58, 95% CI 1.03-2.43, p=0.038) in TCF7L2. The risk alleles of the SNPs rs7756992 and rs7754840 in CDKAL1; rs10811661 in the CDKN2A-CDKN2B region; and rs1111875, rs5015480 and rs7923837 in HHEX were associated with significant decreases in the insulin AUC during a 100 g OGTT performed at the time of diagnosis of GDM. Conclusions/interpretation Some of the type 2 diabetesassociated genetic variants that were discovered in the recent GWA studies are also associated with GDM in Koreans.

Analysis of the haplotype and linkage disequilibrium of PPARγ gene polymorphisms rs3856806, rs12490265, rs1797912, and rs1175543 among patients with metabolic syndrome in Kazakh of Xinjiang Province

“…Numerous genes related to fatty acid transport and metabolism require regulation of the PPARγ gene at the transcriptional level. PPARγ gene polymorphisms are reportedly relevant to the components of MS; however, other studies have shown different results (Hu et al, 2004;Chen et al, 2006;Jaziri et al, 2006;Gaulton et al, 2008;Cho et al, 2009;Gallicchio et al, 2009;Matsuo et al, 2009;Bego et al, 2011). Understanding the relationship of the high incidence of MS and PPARγ gene polymorphisms is important for determining the mechanism of MS occurrence and development as well as for identifying molecular markers that could be used for early diagnosis and prognosis.…”

“…PPARγ genetic polymorphisms include rs3856806, rs12490265, rs1797912, and rs1175543, which may be associated with MS. Differences exist among ethnicities and regions with respect to PPARγ gene polymorphisms; however, the results of various studies are not consistent regarding the extent in or causes of these differences (Hu et al, 2004;Chen et al, 2006;Jaziri et al, 2006;Gaulton et al, 2008;Cho et al, 2009;Gallicchio et al, 2009;Matsuo et al, 2009;Bego et al, 2011). Because the geographical and ethnic characteristics of members of the Xinjiang population can be used to reveal the cause of MS and thus provide a theoretical basis for its underlying genetic mechanism, this study examined the relationship of the PPARγ rs3856806, rs12490265, rs1797912, and rs1175543 polymorphisms, their haplotypes, and linkage disequilibrium with MS in Kazakh subjects in Xinxiang.…”

Impact of common type 2 diabetes risk gene variants on future type 2 diabetes in the non-diabetic population in Korea

“…11,24 Additionally, several studies reported that the KCNQ1 gene was related to diabetes in the Korean population. [19][20][21] Most of these studies used a case subject-control subject design that tended to overestimate the risk of an SNP because case subjects and control subjects usually represented two extremes of the distribution of glucose tolerance. Therefore, we investigated whether the SNPs may indeed increase the risk of future T2DM in non-diabetic subjects.…”

“…Previously, several reports showed that the common genetic variants analyzed in our study were significantly associated with diabetes in the Korean population. [19][20][21] Previous studies suggested that common variants in CDKAL1, SCL3A08, TCF7L2 and PPARG were also significantly associated with increased risk of future diabetes. 12,27 These discrepancies may be explained by the differences in the frequency and loci of genetic variants, ethnicity, population characteristics and follow-up durations.…”

“…4,7,[9][10][11] In particular, we selected six genes that showed reproducible associations with T2DM in cross-sectional studies in Korea. [19][20][21][22] The selected genes were as follows: KCNQ1 rs2237892, CDKAL1 rs7554840, CDKN2A/B rs1081161, SCL30A8 rs13266634, TCF7L2 rs7903146 and PPARG rs1801282.…”