Black Carbon Exposures, Blood Pressure, and Interactions with Single Nucleotide Polymorphisms in MicroRNA Processing Genes

摘要

Background Black carbon (BC) is a marker of traffic pollution that has been associated with blood pressure (BP), but findings have been inconsistent. MicroRNAs (miRNAs) are emerging as key regulators of gene expression, but whether polymorphisms in genes involved in processing of miRNAs to maturity influence susceptibility to BC has not been elucidated. Objectives We investigated the association between BC and BP, as well as potential effect modification by single nucleotide polymorphisms (SNPs) in miRNA processing genes. Methods Repeated measures analyses were performed using data from the VA Normative Aging Study. Complete covariate data were available for 789 participants with one to six study visits between 1995 and 2008. In models of systolic and diastolic BP, we examined SNP-by-BC interactions with 19 miRNA-related variants under recessive models of inheritance. Mixed-effects models were adjusted for potential confounders including clinical characteristics, lifestyle, and meteorologic factors. Results A 1-SD increase in BC (0.415 μg/m3) was associated with 3.04 mmHg higher systolic (95% confidence interval (CI), 2.29–3.79) and 2.28 mmHg higher diastolic BP (95% CI, 1.88–2.67). Interactions modifying BC associations were observed with SNPs in the DICER , GEMIN4 , and DiGeorge critical region-8 ( DGCR8 ) genes, and in GEMIN3 and GEMIN4 , predicting diastolic and systolic BP, respectively. Conclusions We observed evidence of effect modification of the association between BP and 7-day BC moving averages by SNPs associated with miRNA processing. Although the mechanisms underlying these associations are not well understood, they suggest a role for miRNA genesis and processing in influencing BC effects.