Atherosclerosis-Related Genes, Low-Level Lead Exposure and Age-Related Hearing Loss: The Normative Aging Study

Abstract

ISEE-0798 Background and Objective: Although age-related hearing loss (ARHL) is one of the leading chronic health conditions experienced by the older adults, little is known about the impact of environmental toxicants and gene-environment interaction. Our recent study has shown associations between cumulative low-level lead exposures and ARHL in a community-based cohort. However, underlying biological mechanisms are still unknown. This study examined whether those associations were modified by genes related to atherosclerosis, including apolipoprotein-E (APOE: rs7412, rs429358, rs405509, rs440446, rs449647, rs769446), lipoprotein lipase (LPL: rs268, rs328, rs1801177), nitric oxide synthase-3 (NOS3: rs1799953, rs1800779), and vascular endothelial growth factor A (VEGFA: rs2010963), given that atherosclerosis which leads to cochlea ischemia and therefore elevate the risk of ARHL may be attributed by lead exposure. Methods: Bone lead levels, markers of cumulative lead exposure, were measured using K-x-ray fluorescence in 563 middle-aged and elderly men in the Normative Aging Study. Pure-tone audiometric examinations were conducted to measure air and bone conduction hearing thresholds. We calculated a pure-tone average (PTA) of thresholds at 500, 1000, 2000, and 4000 Hz. Results: After controlling for potential confounders, an interquartile range increase in tibia lead (14 mg/g) was associated with a 1.7 (95% confidence interval (CI), 0.44, 2.9) dB increase in the air conduction PTA among persons with at least one copy of the minor allele in APOE rs449647, whereas no association was found among persons with homozygous major alleles (−0.85 dB, 95% CI, −2.2, 0.54; P-interaction = 0.005). We also found significant effect modification by APOE rs769446. No effect modification by LPL, NOS3 and VEGFA genetic polymorphisms was found. The results with patella lead and those in the bone conduction PTA were similar but less significant. Conclusion: This study suggests that some SNPs in the promoter region of the APOE gene modify the chronic effects of lead on ARHL.