Polymorphisms of <i>KCNJ11</i> (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population

Koo, Bo Kyung; Cho, Y. M.; Park, B. L.; Cheong, Hyun Sub; Shin, Hyoung Doo; Jang, Hak Chul; Kim, S. Y.; Lee, H. K.; Park, K. S.

doi:10.1111/j.1464-5491.2006.02050.x

Cited by 74 publications

(59 citation statements)

References 34 publications

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“…Two representative SNPs (rs1333040 and rs10757278) close to CDKN2A-CDKN2B that were associated with coronary heart disease and myocardial infarction were also selected [28][29][30]. In addition, rs7903146 and rs12255372 in TCF7L2 [31]; rs5215 and rs5219 in KCNJ11 [32]; and rs3856806 and rs1801282 in PPARG [33] were also genotyped.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2008

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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.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2008

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“…[1][2][3][4] However, a large-scale association study of these genes has not been carried out in the Chinese Han population; and there was much inconsistency in results in East Asian studies before. [5][6][7][8][9] …”

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“…1-4 However, a large-scale association study of these genes has not been carried out in the Chinese Han population; and there was much inconsistency in results in East Asian studies before. [5][6][7][8][9] In this study, 1912 unrelated type 2 diabetes patients and 2041 normal controls (Supplementary methods) were recruited from Shanghai, China, by measuring their clinical characteristics (Supplementary Table 1). Both the SNPs (single nucleotide polymorphisms) mentioned above were genotyped by TaqMan SNP Genotyping Assays on an ABI7900 system (Applied Biosystems, Foster City, CA, USA).…”

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confidence: 99%

“…For meta-analysis, there was no significant heterogeneity (Cochran's Q-test) and publication bias (Egger's test) for rs5219 (P¼0.41 and P¼0.15, respectively) and rs1799854 (P¼0.92 and P¼0.90, respectively). For meta-analysis of the KCNJ11 E23K variant, all eight studies [5][6][7][8][9]11,12 included 7874 cases and 7629 controls and showed a strong significant association (fixed OR 1.15, 95% CI 1.10-1.21, P¼3Â10 À9 , Figure 1a). For the ABCC8 exon16-3t/c variant, all five studies 7,9,13,14 included 4651 cases and 4394 controls and showed no association with type 2 diabetes (fixed OR 1.05, 95% CI 0.99-1.12, P¼0.080, Figure 1b).…”

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confidence: 99%

“…Common polymorphisms in KCNJ11 were detected to be in a strong LD block and the block also extended to the ABCC8 gene in several previous studies; for instance, both ABCC8 S1368A (rs757110) and KCNJ11 rs5215 were in a high level of LD (r 2 40.8) with the E23K variant. 5,7,9 In addition, rs1799854 is located in the 3¢-splice site of the ABCC8 gene and can impair normal splicing. In this study, it is not possible to exclude the ABCC8 gene as a susceptibility gene involved in type 2 diabetes, even though no association was detected for rs1799854 in the East Asian population.…”

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The E23K variation in the KCNJ11 gene is associated with type 2 diabetes in Chinese and East Asian population

et al. 2009

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The genes (ABCC8 and KCNJ11) have a key role in glucose-stimulated insulin secretion and thus have always been considered as excellent susceptibility candidates for involvement in type 2 diabetes. Common polymorphisms (KCNJ11 E23K and ABCC8 exon16-3t/c) in these genes have been reported to be associated with type 2 diabetes in various European-descent populations. However, there were inconsistent results in previous studies in East Asian populations and no large case-control studies have been carried out in the Chinese Han population. In this study, these two variants were genotyped in about 4000 Chinese by using TaqMan technology on an ABI7900 system. A meta-analysis was also used to assess the results of association between the two variants and type 2 diabetes in East Asian populations. Our investigation confirmed the association between the KCNJ11 E23K variant and type 2 diabetes under a recessive model (KK vs EK+EE) in the Chinese Han population (odds ratio (OR)¼1.25, 95% confidence interval (95% CI) 1.04-1.50, P¼0.017). The meta-analysis of East Asian populations also showed a strong significant association of the K allele with diabetes (OR¼1.15, P¼3Â10 À9 ), whereas the exon16-3t/c variant (rs1799854) in ABCC8 showed no significant association. Thus, the common E23K variant is considered as a strong candidate for type 2 diabetes susceptibility across different ethnicities. Keywords: association study; Chinese population; KCNJ11; meta-analysis; type 2 diabetes Type 2 diabetes is a polygenic disorder characterized by defects in insulin secretion and peripheral insulin resistance. The pancreatic b-cell adenosine triphosphate (ATP)-sensitive potassium channel (KATP), which is composed of Kir6.2 subunits (the KCNJ11 gene) and Sur1 subunits (the ABCC8 gene), has a central role in the regulation of glucose-induced insulin secretion by linking signals derived from glucose metabolism to cell membrane depolarization and insulin exocytosis. 1 Mutations in both genes can cause familial persistent hyperinsulinemic hypoglycemia in infancy and permanent neonatal diabetes. The KCNJ11 and ABCC8 genes are located at the same chromosome locus, 11p15.1, and are only 4.5 kb apart. Moreover, the strong linkage disequilibrium (LD) across the KCNJ11 gene also extends into the ABCC8 gene. Two representative common variants (KCNJ11 E23K and ABCC8 exon16-3t/c), which were in different LD blocks, have also been reported to be associated with type 2 diabetes in various ethnic populations, with fairly consistent results for the KCNJ11 E23K variant and conflicting results for the ABCC8 exon16-3t/c variant. [1][2][3][4] However, a large-scale association study of these genes has not been carried out in the Chinese Han population; and there was much inconsistency in results in East Asian studies before. [5][6][7][8][9]

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From Cellular Mechanisms to Physiological Responses

Newman

2019

Cellular Signal Transduction in Toxicology and Pharmacology

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Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population

Abstract: Polymorphisms in KCNJ11 are associated with Type 2 diabetes and also with hypertension in the Korean population.

Cited by 74 publications

References 34 publications

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

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

The E23K variation in the KCNJ11 gene is associated with type 2 diabetes in Chinese and East Asian population

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