Abstract
BackgroundIn 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.MethodsEvaluating 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.ResultsOf 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).ConclusionIn 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.
Highlights
Evaluating a combined cohort of Atherosclerosis Risk in Communities (ARIC) and Jackson Heart Study (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
Caucasians had higher proportions of these risk alleles compared to African Americans
NHLBI further requires the ARIC study and the JHS to maintain the accuracy of this dataset, so both the ARIC study and the JHS Coordinating Centers send modifications to BioLINCC for incorporation as appropriate
Summary
Prior analyses of the Atherosclerosis Risk in Communities (ARIC) Study and Jackson Heart Study (JHS) cohorts have shown low-normal serum potassium (K) to be associated with risk of diabetes, independent of traditional risk factors [1, 2], and that this association is more robust among African Americans than Caucasians [3, 4]. The mechanism for this association remains to be elucidated. We hypothesized that there could be a gene-by-environment interaction between KCNJ11 variation and serum K on diabetes risk
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