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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.

TitleKCNJ11 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.
Publication TypeJournal Article
Year of Publication2018
AuthorsChatterjee R, Davenport CA, Raffield LM, Maruthur N, Lange L, Selvin E, Butler K, Yeh H-C, Wilson JG, Correa A, Edelman D
Secondary AuthorsHauser E
JournalPLoS One
Volume13
Issue8
Paginatione0203213
Date Published2018
ISSN1932-6203
KeywordsAfrican Americans, Atherosclerosis, Biomarkers, Cohort Studies, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Follow-Up Studies, Genetic Variation, Humans, Incidence, Male, Middle Aged, Potassium, Potassium Channels, Inwardly Rectifying, Prospective Studies, Risk Factors
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

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.

DOI10.1371/journal.pone.0203213
Alternate JournalPLoS One
PubMed ID30169531
PubMed Central IDPMC6118367
Grant ListP30 DK096493 / DK / NIDDK NIH HHS / United States
T32 HL129982 / HL / NHLBI NIH HHS / United States
KL2 TR001115 / TR / NCATS NIH HHS / United States
U54 GM115428 / GM / NIGMS NIH HHS / United States
P30 DK079637 / DK / NIDDK NIH HHS / United States