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Wilker, Elissa*; Baccarelli, Andrea*†; Suh, Helen*; Vokonas, Pantel§; Wright, Robert*‡; Schwartz, Joel*‡
*Harvard School of Public Health, Boston, MA, United States; †University of Milan & IRCCS OMPMaRE Foundation, Milan, Italy; ‡Channing Laboratory, Boston, United States; and §VA Medical Center, Boston, MA, United States.
Evidence suggests that black carbon (BC) from traffic pollution contributes significantly to particle-related cardiovascular effects but the underlying mechanisms are unclear. Micro-RNAs (miRNAs) are small non-coding RNAs involved in processes related to angiogenesis, inflammation, and endothelial cell function. However, whether miRNAs mediate cardiovascular effects of particulate has not been examined. We hypothesized that associations between BC and systolic and diastolic blood pressure (SBP and DBP) would be modified by single nucleotide polymorphisms (SNPs) in genes related to miRNA processing.
We used mixed models with random intercepts and adjusted for potential confounders to examine longitudinal associations between BC and BP. Effect modification was assessed by 38 miRNA-related SNPs using dominant models of inheritance.
704 participants provided blood pressure measurements and DNA. Significant interactions with BC predicting both SBP and DBP were observed for rs1834306 in mir100. For example, a 1 SD increase in BC for rs1834306 was associated with 4.2% higher SBP (95% CI: 2.8, 5.5) in wild-type individuals and 2.1% higher SBP (95% CI: 1.3, 2.9) in subjects with the variant. BC was associated with 5.0% higher DBP (95% CI: 3.7, 6.4) and a 3.0% higher DBP (95% CI: 2.3, 3.8) respectively. For SBP models, interactions were also observed for SNPs in GEMIN4, RAN, and AGO1, while in DBP models, we observed interactions with SNPs in GEMIN3, and additional SNPs in GEMIN4. These associations remained significant after adjustment for multiple testing.
We observed independent associations between BP and BC and found that this association may be modified by SNPs related to miRNA processing. Interestingly, effects were particularly strong with SNPs in GEMIN4, which essential to pre-mRNA splicing and assembly of ribonucleoproteins.
© 2009 Lippincott Williams & Wilkins, Inc.
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