Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes |
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| Authors: | Hsieh Yi-Chen Lien Li-Ming Chung Wen-Ting Hsieh Fang-I Hsieh Pei-Fan Wu Meei-Maan Tseng Hung-Pin Chiou Hung-Yi Chen Chien-Jen |
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| Institution: | aSchool of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan;bGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;cSchool of Medicine, Taipei Medical University, Taipei, Taiwan;dDepartment of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan;eDepartment of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan;fGraduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan;gGraduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan;hDepartment of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan;iGenomics Research Center, Academia Sinica, Taipei, Taiwan |
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| Abstract: | Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose–response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 μg/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 μg/l in drinking water and those who carried the PNP A–T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79–23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 μg/l). |
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| Keywords: | Arsenic PNP As3MT GSTO1 GSTO2 Atherosclerosis |
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