Association Studies of Variants in the Genes Involved in Pancreatic β-Cell Function in Type 2 Diabetes in Japanese Subjects

Yokoi, Norihide; Kanamori, Masao; Horikawa, Yukio; Takeda, Jun; Sanke, Tokio; Furuta, Hiroto; Nanjo, Kishio; Mori, Hiroyuki; Kasuga, Masato; Hara, Kazuo; Kadowaki, Takashi; Tanizawa, Yukio; Oka, Yoshitomo; Iwami, Yukiko; Ohgawara, Hisako; Yamada, Yoshio; Seino, Yutaka; Yano, Hideki; Cox, Nancy J.; Seino, Susumu

doi:10.2337/db05-1203

Cited by 91 publications

(70 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Several studies in various ethnic populations have shown association of polymorphisms in genes involved in b-cell development and function with T2D and associated phenotypes. [2][3][4][5][6][7] Importantly, genome-wide association studies have also deciphered associations with loci predominantly involved in b-cell function. 8 Indians have the highest incidence and prevalence of T2D worldwide.…”

Section: Introductionmentioning

confidence: 99%

Association of variants in genes involved in pancreatic β-cell development and function with type 2 diabetes in North Indians

et al. 2011

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Association of variants in genes involved in pancreatic β-cell development and function with type 2 diabetes in North Indians

et al. 2011

View full text Add to dashboard Cite

“…[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] …”

mentioning

confidence: 99%

“…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).…”

mentioning

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).…”

mentioning

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.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2009

View full text Add to dashboard Cite

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]

show abstract

Diabetes in Asia

Chan

Malik²,

Jia³

et al. 2009

JAMA

Self Cite

1,744

675

View full text Add to dashboard Cite

Background Diabetic foot ulcer infection cause great morbidity and mortality among diabetic patients and is a major cause of lower extremity amputation worldwide. This study aimed to determine the profile of aerobic bacteria and their antibiotic sensitivity patterns in diabetic foot infections (DFI) among different Wagner's grades. Methods This study was conducted during December 2017-March 2018 in a Diabetic Center, Sudan. A total of 152 diabetic patients with different grades of foot ulcers were randomly enrolled in the study. The patients were grouped using Wagner's classification. Tissue biopsies and deep swabs were collected from the ulcers for aerobic cultures. The cultured isolates were identified using phenotypic and biochemical properties and their sensitivity to commonly used antibiotics, Colistin, Aikacin, Ciprofloxacin, Augmentin, Ceftazideme, Gentamicin, Clindamycin, Ceftriaxone Meropenum. Cotrimoxazole, Erythomycin, Oxacillin and Vancomycin. Fusidic acid, Imepenem, and Piperacillin was tested using the Kirby Bauer disk diffusion method. Results The mean age of the patients was 54.31 (SD ± 12.1) years, male to female ratio of 8: 1. The mean duration of diabetes was 14 (SD ± 8) years. The ulcers varied in duration from 1 day to 10 years. of 152 samples 181 aerobic bacteria were isolated. Cultures yielded 1-3 isolate per culture. The maximum number was isolated from grade 3 group followed by long standing ulcer LSU group 50.8% and 28% respectively. Polymicrobial infection was higher in LSU (30.4%). The isolates were mostly Gram-negative bacteria. The most frequent were proteus spp. (35.3%), S. aureus MRSA 14.4% and Coliform 12.2% respectively. The most common isolates in grade 3 were P. Mirablis, Staphylococcus and Coliform and in long standing ulcers were P. Mirablis, S. aureus MRSA and Coagulase negative staphylococcus respectively. Conclusion Gram-negative bacteria were more prevalent and the most frequent pathogens were Proteus spp. The

show abstract

Association Studies of Variants in the Genes Involved in Pancreatic β-Cell Function in Type 2 Diabetes in Japanese Subjects

Cited by 91 publications

References 32 publications

Association of variants in genes involved in pancreatic β-cell development and function with type 2 diabetes in North Indians

Association of variants in genes involved in pancreatic β-cell development and function with type 2 diabetes in North Indians

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

Diabetes in Asia

Contact Info

Product

Resources

About