Population Specific Impact of Genetic Variants in KCNJ11 Gene to Type 2 Diabetes: A Case-Control and Meta-Analysis Study

Phani, Nagaraja M.; Guddattu, Vasudeva; Bellampalli, Ravishankara; Seenappa, Venu; Adhikari, Prabha; Nagri, Shivashankara Kaniyoor; D’Souza, Sydney C.; Mundyat, Gopinath P.; Satyamoorthy, Kapaettu; Padmalatha, S

doi:10.1371/journal.pone.0107021

Cited by 42 publications

(28 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fourteen of the novel BP variants identified in the present study reside in loci that were previously reported in GWAS to be associated with lipids 19 , immunologic diseases 20–22 , and metabolic phenotypes 23–25, 29 (Table 2 and Supplementary Table 7). Thirteen of the previously identified BP variants were also linked to non-BP traits/diseases (Supplementary Table 19).…”

Section: Discussionmentioning

confidence: 77%

“…Of the 28 newly identified common variants for BP, 14 were genome-wide significant in prior GWAS of lipids 19 , immunologic disease 20–22 , diabetes 23–25 , kidney function 26 , age at menarche 27 , resting heart rate 28 , waist-hip ratio 29 , and homocysteine concentration 30 , but not BP (Table 2 and Supplementary Table 7). Six additional variants were reported for several phenotypes (Table 2) in previous candidate gene, patent filing or GWAS studies, but their P values were not specified or did not reach the genome-wide significance level 31–36 .…”

Section: New Loci Associated With Bp By Single Variant Analysesmentioning

confidence: 99%

See 1 more Smart Citation

Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

Liu¹,

Kraja²,

Smith³

et al. 2016

Nat Genet

245

176

View full text Add to dashboard Cite

Meta-analyses of association results for blood pressure using exome-centric single-variants and gene-based tests identified 31 novel loci in discovery among 146,562 individuals with follow-up and meta-analysis in 180,726 additional individuals (Ntotal=327,288). These blood pressure loci are enriched for known cardiometabolic trait variants. Associations were also observed for the aggregation of rare/low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure loci suggests new therapeutic strategies for hypertension emphasizing a link with cardiometabolic risk.

show abstract

Section: Discussionmentioning

confidence: 77%

Section: New Loci Associated With Bp By Single Variant Analysesmentioning

confidence: 99%

Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

Liu¹,

Kraja²,

Smith³

et al. 2016

Nat Genet

245

176

View full text Add to dashboard Cite

show abstract

“…KCNJ11 , encoding a member of the potassium channel gene family, contributes to insulin secretion. Previous reports showed that rs5215 is associated with the development of type 2 diabetes mellitus. High mobility group protein 20A ( HMG20A ) was related to the development of type 2 diabetes mellitus in European individuals, and it might contribute to insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic characteristics of abnormal glucose tolerance in Japanese women in the first year after gestational diabetes mellitus

Kasuga

Miyakoshi

Tajima

et al. 2018

J of Diabetes Invest

View full text Add to dashboard Cite

Aims/Introduction Risk factors of type 2 diabetes mellitus in Japanese women with recent gestational diabetes mellitus are unknown. The objective of the present study was to investigate the clinical and genetic characteristics associated with postpartum abnormal glucose tolerance in Japanese women with gestational diabetes mellitus. Materials and Methods A total of 213 Japanese women with recent gestational diabetes mellitus who underwent a postpartum 2‐h oral glucose tolerance test were investigated. The association between antepartum clinical characteristics and postpartum abnormal glucose tolerance (diabetes or prediabetes based on the Japan Diabetes Society criteria) was examined. Frequencies of 45 known type 2 diabetes mellitus‐associated genetic variants were also compared between women with and without postpartum abnormal glucose tolerance. Results A total of 59 women showed postpartum abnormal glucose tolerance (prediabetes, n = 51; diabetes, n = 8). Plasma glucose levels at 1 or 2 h, the insulinogenic index and the insulin secretion‐sensitivity index‐2 of the antepartum oral glucose tolerance test were independent of postpartum abnormal glucose tolerance risk factors ( P = 0.006, P = 0.00002, P = 0.01 and P = 0.006, respectively). Four genetic variants (rs266729 [ ADIPOQ ], rs6017317 [ HNF 4A ], rs5215 [ KCNJ 11 ] and rs7177055 [ HMG 20A ]) showed a nominally significant association with postpartum abnormal glucose tolerance ( P < 0.05, respectively). Among these, three were related to insulin secretion. Postpartum abnormal glucose tolerance risk significantly increased with increasing risk‐allele number ( P = 0.0005; odds ratio 1.91). Conclusions Clinical features and genetic variants related to impaired insulin secretion are risk factors of postpartum abnormal glucose tolerance in Japanese women with recent gestational diabetes mellitus.

show abstract

“…Increased numbers of patients in study populations have revealed an association between this polymorphic marker and the T2DM development [31][32][33][34][35][36][37]. Despite the fact that this association was found by other investigators [38], the K23 allele has been associated with the increased risk gene expression [11].…”

Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population (v0.2)"

2017

View full text Add to dashboard Cite

Background. The association of type 2 diabetes mellitus (T2DM) with the KCNJ11, CDKAL1, SLC30A8, CDKN2B, and FTO genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes. Methods. The study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs) of the genes using real-time PCR (TaqMan assays). HOMA-IR and HOMA-β were used to measure insulin resistance and β-cell secretory function, respectively. Results. The analysis of the frequency distribution of polymorphic markers for genes KCNJ11, CDKAL1, SLC30A8 and CDKN2B showed statistically significant associations with T2DM in the Russian population. The association between the FTO gene and T2DM was not statistically significant. The polymorphic markers rs5219 of the KCNJ11 gene, rs13266634 of the SLC30A8 gene, rs10811661 of the CDKN2B gene and rs9465871, rs7756992 and rs10946398 of the CDKAL1 gene showed a significant association with impaired glucose metabolism or impaired β-cell function. Conclusion. In the Russian population, genes, which affect insulin synthesis and secretion in the β-cells of the pancreas, play a central role in the development of T2DM.

show abstract

Population Specific Impact of Genetic Variants in KCNJ11 Gene to Type 2 Diabetes: A Case-Control and Meta-Analysis Study

Cited by 42 publications

References 34 publications

Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

Clinical and genetic characteristics of abnormal glucose tolerance in Japanese women in the first year after gestational diabetes mellitus

Peer Review #1 of "Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population (v0.2)"

Contact Info

Product

Resources

About