Arsenic Exposure, Null Genotypes of Glutathione S-Transferase M1,T1 and P1, and Risk of Carotid Atherosclerosis among Residents in the Lanyang Basin of Taiwan

摘要

In order to evaluate the synergistic effects of arsenic exposure through drinking water and genetic polymorphisms of GST M1, T1, and P1 on the risk of carotid atherosclerosis, a total of 605 residents who participated physical examination of arsenic-induced health effects held in Lanyang Basin were recruited as study subjects. A standardized personal interview based on a structured questionnaire was carried out to obtain information on duration of well water consumption, so-ciodemographic characteristics, cigarette smoking, alcohol drinking, as well as personal and family history of hypertension, diabetes and cerebrovascular disease. Well water samples were collected during the home interview. Hydride generator combined with flame atomic absorption spectro-metry was used to determine the arsenic concentration in these samples. Whole blood samples were collected and centrifuged to separate buffy coat. DNA was then purified from buffy coat and stored at -20℃ until genotyping. PCR was used for genotyping GSTM1 and GSTT1. PCR-RFLP was also carried out to determine the genetic polymorphisms of GST P1. Intimal-medial thickness (IMT) of arterial walls was measured by B-mode real-time ultrasound as an index of atherosclerosis. Plaque score was also used as an index of atherosclerosis. Logistic regression analysis was used to estimate age-sex-adjusted odds ratio and 95% confidence interval. Age was a major risk for the development of carotid atherosclerosis, showing a significant dose-response relationship. Compared with the youngest age group, the significant odds ratios of 5.9 and 2.3 were observed for the oldest and middle age groups, respectively. Significant risk for occurrence of carotid atherosclerosis was also observed among hypertension patients with age-sex-adjusted odds ratio of 2.4. Significant age-sex-adjusted odds ratios of risk of carotid atherosclerosis were observed in exposure groups with arsenic concentration in well water greater than 50 μg/l, showing odds ratio of 2.5. Moreover, study subjects with cumulative arsenic exposure greater than 1.0 mg/l-year also had significant age-sex-adjusted risk of developing carotid atherosclerosis. A significant higher age-sex-adjusted odds ratio of 2.0 for the development of carotid atherosclerosis was observed among study subjects with genotypes of W/M and M/M for GSTP1. A significant dose-response relationship was observed between risk of carotid atherosclerosis and arsenic exposure indices of arsenic concentration in well water and cumulative arsenic exposure among study subjects with null genotype of GSTM1, T1 and with W/M or M/M genotype of GSTP1. In conclusion, a significant effect on the risk of carotid atherosclerosis was observed among study subjects with arsenic exposure and with genotypes of W/M and M/M. In addition, significant synergistic effects on the risk for development of carotid atherosclerosis were also found between arsenic exposure and various genotypes of GST M1.