Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population

Abstract

According to recent genome-wide association studies, a number of single nucleotide polymorphisms (SNPs) are reported to be associated with type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the association among the polymorphisms of SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1 and KCNQ1 and the risk of T2DM in the Korean population. This study was based on a multicenter casecontrol study, including 908 patients with T2DM and 502 non-diabetic controls. We genotyped rs13266634, rs1111875, rs10811661, rs4402960, rs8050136, rs734312, rs7754840 and rs2237892 and measured the body weight, body mass index and fasting plasma glucose in all patients and controls. The strongest association was found in a variant of CDKAL1 [rs7754840, odds ratio (OR) = 1.77, 95% CI = 1.50-2.10, p = 5.0 9 10-11 ]. The G allele of rs1111875 (OR = 1.43, 95% CI = 1.18-1.72, p = 1.8 9 10 -4 ) in HHEX), the T allele of rs10811661 (OR = 1.47, 95% CI = 1.23-1.75, p = 2.1 9 10 -5 ) in CDKN2A/B) and the C allele of rs2237892 (OR = 1.31, 95% CI = 1.10-1.56, p = 0.003) in KCNQ1 showed significant associations with T2DM. Rs13266634 (OR = 1.19, 95% CI = 1.00-1.42, p = 0.045) in SLC30A8 showed a nominal association with the risk of T2DM, whereas SNPs in IGF2BP2, FTO and WFS1 were not associated. In conclusion, we have shown that SNPs in HHEX, CDKN2A/B, CDKAL1, KCNQ1 and SLC30A8 confer a risk of T2DM in the Korean population.

Heterogeneity of genetic associations of CDKAL1 and HHEX with susceptibility of type 2 diabetes mellitus by gender

“…Especially, they were all located within CDKAL1 gene except for an intergenic variant of rs5015480 near HHEX gene. The association of the CDKAL1 gene concurred with the results from previous studies with American, 1 British, 5 French, 3 Danish, 4 Finnish, 2 Swedish, 1 Icelandic, 4 Korean, 9 Japanese, 10 and Chinese [11][12][13] populations. The significantly associated variants of the gene in the current study were specifically corresponding to those found in previous studies of Horikawa et al 14 and Wu et al 11 for rs7756992 and Zeggini et al 5 and Wu et al 11 for rs9465871 and rs10946398, respectively.…”

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

“…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.…”

“…The estimated powers of our study were 97%, 72%, 98% and 39% for rs2237892 (KCNQ1), rs7754840 (CDKAL1), rs10811661 (CDKN2A/B) and rs13266634 (SLC30A8), respectively, in the recessive genetic model and 92%, 84%, 85%, 61%, 85% and 41% for rs2237892 (KCNQ1), rs7754840 (CDKAL1), rs10811661 (CDKN2A/B), rs13266634 (SLC30A8), rs7903146 (TCF7L2) and rs1801282 (PPARG), respectively, in the dominant genetic model, based on the reference odds ratios and allele frequencies from previous studies. 15,21,23 Po0.05 was considered statistically significant.…”

Management of Diabetes in Organ Transplant Patients

“…본 저자의 연구결과 대부 분의 제2형 당뇨병 관련 유전자 즉 TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, KCNQ1 유전자 변이가 이식 후 당뇨병 발생에서도 유의한 연관관계를 보였다 [14]. TCF7L2 rs7903146 [14,15], SLC30A8 rs13266634 [14,16], HHEX rs1111875, HHEX rs7923837, HHEX rs5015480, CDKAL1 rs10946398, CDKN2A/B rs10811661 [14,17] [10,13,30]. Calcineurin억제제는 인슐린 저항성을 증가시 키는 부분도 있지만 췌장의 베타세포에 독성을 나타내어 인슐린 분비능을 저하시킴으로써 혈당을 상승시키는 부분 이 더 중요할 수 있다 [31].…”