Exposure to arsenic (As) increases cardiovascular risk. The purpose of this study was to evaluate the relationship between As and intima-media thickness (IMT) in the common carotid artery and common genetic variants in genes implicated in As metabolism (ASIIIMT Met287Thr, GSTT1+/-, and GSTM1+/-) and DNA repair (hOGG1 Ser326Cys and XRCC1 Arg399Ser). Two hundred and fourteen healthy volunteers, age 20-46, were recruited in four zones polluted by As. Urine samples were tested for total As, inorganic As (iAs), monomethylarsinic (MMA), and dimethylarsinic acid (DMA). Primary and secondary methylation index (PMI, SMI) were computed as MMA/iAs and DMA/MMA. Common carotid artery scans were obtained by high-resolution ultrasound. There was no correlation between IMT and total As, iAs, iAs + MMA + DMA, PMI, or SMI. However, the increase of IMT with age was higher than that observed in the healthy population, both in males (6.25 vs. 5.20 μm/year) and, to a lesser extent, in females (5.05 vs. 4.97 μm/year). After correction for age and gender, subjects with a high urinary As level (≥3.86 μg/L) and carriers of the GSTT1-positive (+) genotype also had higher IMT than those with a low urinary level and the GSTT1-null (-) genotype (0.56 [0.48-0.64] vs. 0.53 [0.44-0.62] mm, p = 0.010). The analysis hints at faster vascular aging as compared to the healthy population. Our findings also suggested that GSTT1 and hOGG1 gene polymorphisms might play an important role in the individual risk of As-induced carotid atherosclerosis.
Keywords: Arsenic; Atherosclerosis; Carotid intima-media thickness; Environmental pollution; Genetic susceptibility; Imaging biomarkers.