Association between genetic polymorphisms of arsenic metabolic enzymes and carotid atherosclerosis

• Main Authors: Pei-Fan, Hsieh, 謝佩帆
• Other Authors: Hung-Yi Chiou
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/69808713860012738793

碩士 === 臺北醫學大學 === 公共衛生學研究所 === 97 === Atherogenesis is a pathophysiological process, which is characterized with the progression from inflammation and smooth muscle cell proliferation to late stage of thrombotic and fibrotic obliterations of the vessels. Level of oxidative stress would increase in human body after long-term exposure to arsenic through drinking well water. However, individual susceptibility to arsenic-induced carotid atherosclerosis were different due to various capability of arsenic metabolism. The aim of this study was to identify the relationship between carotid atherosclerosis and genetic polymorphisms of arsenic related metabolic genes including purine nucleoside phosphorylase（PNP）, glutathione S-transferase omega（GSTO1, GSTO2）, arsenite methyltransferase （As3MT）. A total of 863 residents aged equal and greater than 40 years and lived in Lanyan Basin were recruited in this study. Among them, 384 subjects were identified as cases based on physician’s diagnosis. All subjects were interviewed by well-trained research assistants to collect questionnaire data including demographic characteristics and serum biochemistry indices. Genetic polymorphisms of PNP, GSTO1, GSTO2 and As3MT were detected by PCR-RFLP. Logistic regression model was used to estimate odds ratio （OR）and 95% confidence interval（CI）of various risk factors of carotid atherosclerosis. Our results showed that subjects with the T allele of PNP Gly51Ser or Pro57Pro had significantly increased risk of carotid atherosclerosis（OR=1.3 and 1.6）. A significantly increased risk of carotid atherosclerosis was also found in subjects with the risk haplotypes and diplotypes of PNP（OR=1.5 and 1.6）. Those who with risk PNP haplotypes and either had ingested well water contained arsenic level> 50μg/L or had cumulative arsenic exposure>1.66 mg/L*year would have elevated 2.3-fold risk of carotid atherosclerosis. Dose-response relationships between increased risk haplotypes of PNP and risk of carotid atherosclerosis were observed among subjects with either drank well water contained arsenic level>50μg/L or with cumulative arsenic exposure>1.66 mg/L*year. A highest risk of carotid atherosclerosis was also found in subjects without hypertension and diabetes mellitus. In conclusion, this study provide the strong evidence that genetic polymorphisms of PNP gene was associated with carotid atherosclerosis. Prominent risk of carotid atherosclerosis were also found among study subjects with risk haplotypes of PNP, high exposure to arsenic and without hypertension and diabetes mellitus.