Black carbon exposures, blood pressure and interactions with SNPs in microRNA processing genes

Background: Black carbon is a marker of traffic pollution which has been associated with blood pressure (BP), although findings have been inconsistent. MicroRNAs are emerging as key regulators of gene expression, but whether polymorphisms in genes involved in processing of microRNAs to maturity influence susceptibility to black carbon has not been elucidated. Objectives: We investigated the association between black carbon and BP, as well as potential effect modification by single nucleotide polymorphisms (SNPs) in microRNA processing genes. Methods: Repeated measures analyses were performed using data from Normative Aging Study. Complete covariate data were available for 789 participants with 1-6 study visits between 1995 and 2008. In models of systolic and diastolic BP we examined SNP-by-black carbon interactions with 19 microRNA-related variants under recessive models of inheritance. Mixed-effects models were adjusted for potential confounders including clinical characteristics, lifestyle and meteorological factors. Results: A 1 standard deviation increase in black carbon (0.415 microg/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 black carbon associations were observed with SNPs in the DICER, GEMIN4, and 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 black carbon moving averages by SNPs associated with miRNA processing. While the mechanisms underlying these associations are not well understood, they suggest a role for miRNA genesis and processing in influencing black carbon effects.