Gene-Arsenic Interaction In Longitudinal Changes Of Blood Pressure: Findings From The Health Effects Of Arsenic Longitudinal Study

Abstract

Cross-sectional studies suggest that high levels of arsenic (As) exposure are related to increases in blood pressure (BP). However, studies examining the relationship between As exposure and longitudinal change in BP are lacking. Evidence of whether genetic susceptibility can play a role in As's effect on BP is also limited. In this study, we evaluated the association between As exposure and longitudinal change in BP in 10,853 participants in the Health Effects of As Longitudinal Study (HEALS), over approximately 7 years of follow-up. Arsenic exposure was measured in well water and urine samples at baseline. Mixed effect models were used to estimate the association of baseline well and urinary As with annual change in systolic (SBP) and diastolic (DBP) BP over the follow-up. In a subset of 1137 subjects with genotyping data on 235 SNPs in 18 genes related to As metabolism, oxidative stress and endothelial function, we assessed gene-As interaction in longitudinal BP changes. Every 100µg/L difference in baseline well As was significantly associated with a greater annual increase of 0.11 (95% CI 0.05-0.16) mmHg in SBP and 0.05 (95% CI 0.02-0.08) mmHg in DBP. Similar increases in SBP and DBP were observed in relation to baseline urinary As. In the subset, we observed a significant interaction between 44 SNPs with As for one or more longitudinal BP measures (SBP, DBP, pulse pressure (PP)). The interaction between CYBA rs3794624 and well As on annual PP change remained significant after correction for multiple comparisons (p=0.05). Among individuals with the rs3794624 variant genotype, well As was associated with a 2.23 mmHg (95% CI 1.14-3.32) greater annual increase in PP, while among those with the wild type, well As was associated with a 0.13 mmHg (95% CI 0.02-0.23) greater annual increase in PP. Our results suggest that long-term As exposure may increase BP more rapidly over time. Furthermore, genetic variability may contribute to As-associated BP increases over time.