KCNJ11 variants and their effect on the association between serum potassium and diabetes risk in the Atherosclerosis Risk in Communities (ARIC) Study and Jackson Heart Study (JHS) cohorts

Ranee Chatterjee, Clemontina A. Davenport, Laura M. Raffield, Nisa Maruthur, Leslie Lange, Elizabeth Selvin, Kenneth Butler, Hsin Chieh Yeh, James G. Wilson, Adolfo Correa, David Edelman, Elizabeth Hauser

Research output: Contribution to journalArticle

Abstract

Background In the Atherosclerosis Risk in Communities (ARIC) Study and Jackson Heart Study (JHS) cohorts, serum potassium (K) is an independent predictor of diabetes risk, particularly among African-American participants. Experimental studies show that serum K levels affects insulin secretion. The KCNJ11 gene encodes for a K channel that regulates insulin secretion and whose function is affected by serum K levels. Variants in KCNJ11 are associated with increased diabetes risk. We hypothesized that there could be a gene-by-environment interaction between KCNJ11 variation and serum K on diabetes risk. Methods Evaluating a combined cohort of ARIC and JHS participants, we sought to determine if KCNJ11 variants are risk factors for diabetes; and if KCNJ11 variants modify the association between serum K and diabetes risk. Among participants without diabetes at baseline, we performed multivariable logistic regression to determine the effect of serum K, KCNJ11 variants, and their interactions on the odds of incident diabetes mellitus over 8–9 years in the entire cohort and by race. Results Of 11,812 participants, 3220 (27%) participants developed diabetes. 48% and 47% had 1 or 2 diabetes risk alleles of rs5215 and rs5219, respectively. Caucasians had higher proportions of these risk alleles compared to African Americans (60% vs 17% for rs5215 and 60% vs 13% for rs5219, p<0.01). Serum K was a significant independent predictor of incident diabetes. Neither rs5215 nor rs5219 was associated with incident diabetes. In multivariable models, we found no statistically significant interactions between race and either rs5215 or rs5219 (P-values 0.493 and 0.496, respectively); nor between serum K and either rs5215 or rs5219 on odds of incident diabetes (P-values 0.534 and 0.687, respectively). Conclusion In this cohort, rs5215 and rs5219 of KCNJ11 were not significant predictors of incident diabetes nor effect modifiers of the association between serum K and incident diabetes.

Original languageEnglish (US)
Article numbere0203213
JournalPLoS One
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2018

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Medical problems
atherosclerosis
cohort studies
diabetes
Atherosclerosis
Potassium
Cohort Studies
heart
potassium
Serum
African Americans
insulin secretion
Alleles
Insulin
Gene-Environment Interaction
Genes
alleles
Diabetes Mellitus
modifiers (genes)
Logistic Models

ASJC Scopus subject areas

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

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KCNJ11 variants and their effect on the association between serum potassium and diabetes risk in the Atherosclerosis Risk in Communities (ARIC) Study and Jackson Heart Study (JHS) cohorts. / Chatterjee, Ranee; Davenport, Clemontina A.; Raffield, Laura M.; Maruthur, Nisa; Lange, Leslie; Selvin, Elizabeth; Butler, Kenneth; Yeh, Hsin Chieh; Wilson, James G.; Correa, Adolfo; Edelman, David; Hauser, Elizabeth.

In: PLoS One, Vol. 13, No. 8, e0203213, 01.08.2018.

Research output: Contribution to journalArticle

Chatterjee, Ranee ; Davenport, Clemontina A. ; Raffield, Laura M. ; Maruthur, Nisa ; Lange, Leslie ; Selvin, Elizabeth ; Butler, Kenneth ; Yeh, Hsin Chieh ; Wilson, James G. ; Correa, Adolfo ; Edelman, David ; Hauser, Elizabeth. / KCNJ11 variants and their effect on the association between serum potassium and diabetes risk in the Atherosclerosis Risk in Communities (ARIC) Study and Jackson Heart Study (JHS) cohorts. In: PLoS One. 2018 ; Vol. 13, No. 8.
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abstract = "Background In the Atherosclerosis Risk in Communities (ARIC) Study and Jackson Heart Study (JHS) cohorts, serum potassium (K) is an independent predictor of diabetes risk, particularly among African-American participants. Experimental studies show that serum K levels affects insulin secretion. The KCNJ11 gene encodes for a K channel that regulates insulin secretion and whose function is affected by serum K levels. Variants in KCNJ11 are associated with increased diabetes risk. We hypothesized that there could be a gene-by-environment interaction between KCNJ11 variation and serum K on diabetes risk. Methods Evaluating a combined cohort of ARIC and JHS participants, we sought to determine if KCNJ11 variants are risk factors for diabetes; and if KCNJ11 variants modify the association between serum K and diabetes risk. Among participants without diabetes at baseline, we performed multivariable logistic regression to determine the effect of serum K, KCNJ11 variants, and their interactions on the odds of incident diabetes mellitus over 8–9 years in the entire cohort and by race. Results Of 11,812 participants, 3220 (27{\%}) participants developed diabetes. 48{\%} and 47{\%} had 1 or 2 diabetes risk alleles of rs5215 and rs5219, respectively. Caucasians had higher proportions of these risk alleles compared to African Americans (60{\%} vs 17{\%} for rs5215 and 60{\%} vs 13{\%} for rs5219, p<0.01). Serum K was a significant independent predictor of incident diabetes. Neither rs5215 nor rs5219 was associated with incident diabetes. In multivariable models, we found no statistically significant interactions between race and either rs5215 or rs5219 (P-values 0.493 and 0.496, respectively); nor between serum K and either rs5215 or rs5219 on odds of incident diabetes (P-values 0.534 and 0.687, respectively). Conclusion In this cohort, rs5215 and rs5219 of KCNJ11 were not significant predictors of incident diabetes nor effect modifiers of the association between serum K and incident diabetes.",
author = "Ranee Chatterjee and Davenport, {Clemontina A.} and Raffield, {Laura M.} and Nisa Maruthur and Leslie Lange and Elizabeth Selvin and Kenneth Butler and Yeh, {Hsin Chieh} and Wilson, {James G.} and Adolfo Correa and David Edelman and Elizabeth Hauser",
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T1 - KCNJ11 variants and their effect on the association between serum potassium and diabetes risk in the Atherosclerosis Risk in Communities (ARIC) Study and Jackson Heart Study (JHS) cohorts

AU - Chatterjee, Ranee

AU - Davenport, Clemontina A.

AU - Raffield, Laura M.

AU - Maruthur, Nisa

AU - Lange, Leslie

AU - Selvin, Elizabeth

AU - Butler, Kenneth

AU - Yeh, Hsin Chieh

AU - Wilson, James G.

AU - Correa, Adolfo

AU - Edelman, David

AU - Hauser, Elizabeth

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Background In the Atherosclerosis Risk in Communities (ARIC) Study and Jackson Heart Study (JHS) cohorts, serum potassium (K) is an independent predictor of diabetes risk, particularly among African-American participants. Experimental studies show that serum K levels affects insulin secretion. The KCNJ11 gene encodes for a K channel that regulates insulin secretion and whose function is affected by serum K levels. Variants in KCNJ11 are associated with increased diabetes risk. We hypothesized that there could be a gene-by-environment interaction between KCNJ11 variation and serum K on diabetes risk. Methods Evaluating a combined cohort of ARIC and JHS participants, we sought to determine if KCNJ11 variants are risk factors for diabetes; and if KCNJ11 variants modify the association between serum K and diabetes risk. Among participants without diabetes at baseline, we performed multivariable logistic regression to determine the effect of serum K, KCNJ11 variants, and their interactions on the odds of incident diabetes mellitus over 8–9 years in the entire cohort and by race. Results Of 11,812 participants, 3220 (27%) participants developed diabetes. 48% and 47% had 1 or 2 diabetes risk alleles of rs5215 and rs5219, respectively. Caucasians had higher proportions of these risk alleles compared to African Americans (60% vs 17% for rs5215 and 60% vs 13% for rs5219, p<0.01). Serum K was a significant independent predictor of incident diabetes. Neither rs5215 nor rs5219 was associated with incident diabetes. In multivariable models, we found no statistically significant interactions between race and either rs5215 or rs5219 (P-values 0.493 and 0.496, respectively); nor between serum K and either rs5215 or rs5219 on odds of incident diabetes (P-values 0.534 and 0.687, respectively). Conclusion In this cohort, rs5215 and rs5219 of KCNJ11 were not significant predictors of incident diabetes nor effect modifiers of the association between serum K and incident diabetes.

AB - Background In the Atherosclerosis Risk in Communities (ARIC) Study and Jackson Heart Study (JHS) cohorts, serum potassium (K) is an independent predictor of diabetes risk, particularly among African-American participants. Experimental studies show that serum K levels affects insulin secretion. The KCNJ11 gene encodes for a K channel that regulates insulin secretion and whose function is affected by serum K levels. Variants in KCNJ11 are associated with increased diabetes risk. We hypothesized that there could be a gene-by-environment interaction between KCNJ11 variation and serum K on diabetes risk. Methods Evaluating a combined cohort of ARIC and JHS participants, we sought to determine if KCNJ11 variants are risk factors for diabetes; and if KCNJ11 variants modify the association between serum K and diabetes risk. Among participants without diabetes at baseline, we performed multivariable logistic regression to determine the effect of serum K, KCNJ11 variants, and their interactions on the odds of incident diabetes mellitus over 8–9 years in the entire cohort and by race. Results Of 11,812 participants, 3220 (27%) participants developed diabetes. 48% and 47% had 1 or 2 diabetes risk alleles of rs5215 and rs5219, respectively. Caucasians had higher proportions of these risk alleles compared to African Americans (60% vs 17% for rs5215 and 60% vs 13% for rs5219, p<0.01). Serum K was a significant independent predictor of incident diabetes. Neither rs5215 nor rs5219 was associated with incident diabetes. In multivariable models, we found no statistically significant interactions between race and either rs5215 or rs5219 (P-values 0.493 and 0.496, respectively); nor between serum K and either rs5215 or rs5219 on odds of incident diabetes (P-values 0.534 and 0.687, respectively). Conclusion In this cohort, rs5215 and rs5219 of KCNJ11 were not significant predictors of incident diabetes nor effect modifiers of the association between serum K and incident diabetes.

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