Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes: A case-control and meta-analysis study

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background and Objectives: Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis.

Results: KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P= 0.04) and higher body mass index (BMI) (P=0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR =0.98, 95% CI=0.83-1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians.

Conclusion: KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.

Methods: A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochran's Q, I2 statistics were used to study heterogeneity between the eligible studies.

Original languageEnglish
Article numbere107021
JournalPLoS One
Volume9
Issue number9
DOIs
Publication statusPublished - 23-09-2014

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Medical problems
noninsulin-dependent diabetes mellitus
meta-analysis
Type 2 Diabetes Mellitus
Meta-Analysis
Genes
Population
genes
Polymorphism
systematic review
genetic polymorphism
Case-Control Studies
confidence interval
Confidence Intervals
Inwardly Rectifying Potassium Channel
insulin secretion
case-control studies
Age of Onset
odds ratio
Haplotypes

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Phani, Nagaraja M. ; Guddattu, Vasudeva ; Bellampalli, Ravishankara ; Seenappa, Venu ; Adhikari, Prabha ; Nagri, Shivashankara K. ; D'Souza, Sydney C. ; Mundyat, Gopinath P. ; Satyamoorthy, Kapaettu ; Rai, Padmalatha S. / Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes : A case-control and meta-analysis study. In: PLoS One. 2014 ; Vol. 9, No. 9.
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abstract = "Background and Objectives: Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis.Results: KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P= 0.04) and higher body mass index (BMI) (P=0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR =0.98, 95{\%} CI=0.83-1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians.Conclusion: KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.Methods: A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95{\%} confidence interval (CI) was used to assess the association strength. Cochran's Q, I2 statistics were used to study heterogeneity between the eligible studies.",
author = "Phani, {Nagaraja M.} and Vasudeva Guddattu and Ravishankara Bellampalli and Venu Seenappa and Prabha Adhikari and Nagri, {Shivashankara K.} and D'Souza, {Sydney C.} and Mundyat, {Gopinath P.} and Kapaettu Satyamoorthy and Rai, {Padmalatha S.}",
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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 K.; D'Souza, Sydney C.; Mundyat, Gopinath P.; Satyamoorthy, Kapaettu; Rai, Padmalatha S.

In: PLoS One, Vol. 9, No. 9, e107021, 23.09.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes

T2 - A case-control and meta-analysis study

AU - Phani, Nagaraja M.

AU - Guddattu, Vasudeva

AU - Bellampalli, Ravishankara

AU - Seenappa, Venu

AU - Adhikari, Prabha

AU - Nagri, Shivashankara K.

AU - D'Souza, Sydney C.

AU - Mundyat, Gopinath P.

AU - Satyamoorthy, Kapaettu

AU - Rai, Padmalatha S.

PY - 2014/9/23

Y1 - 2014/9/23

N2 - Background and Objectives: Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis.Results: KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P= 0.04) and higher body mass index (BMI) (P=0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR =0.98, 95% CI=0.83-1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians.Conclusion: KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.Methods: A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochran's Q, I2 statistics were used to study heterogeneity between the eligible studies.

AB - Background and Objectives: Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis.Results: KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P= 0.04) and higher body mass index (BMI) (P=0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR =0.98, 95% CI=0.83-1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians.Conclusion: KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.Methods: A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochran's Q, I2 statistics were used to study heterogeneity between the eligible studies.

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