Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam

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• 作者：Tetsuro Agusa ; Hisato Iwata ; Junko Fujihara ; Takashi Kunito ; Haruo Takeshita ; Tu Binh Minh ; Pham Thi Kim Trang ; Pham Hung Viet ; Shinsuke Tanabe
• 关键词：Arsenic ; Glutathione S-transferase ω ; 1 (GSTO1) ; GST ω ; 2 (GSTO2) ; GST π ; 1 (GSTP1) ; GST μ ; 1 (GSTM1) ; GST θ ; 1 (GSTT1) ; Genetic polymorphism ; Vietnam
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2010
• 出版时间：1 February 2010
• 年：2010
• 卷：242
• 期：3
• 页码：352-362
• 全文大小：496 K

文摘

To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for GST ω1 (GSTO1) Ala140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST ω2 (GSTO2) Asn142Asp, GST π1 (GSTP1) Ile105Val, GST μ1 (GSTM1) wild/null, and GST θ1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu155del hetero type showed higher urinary concentration of As^V than the wild homo type. Higher percentage of DMA^V in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As^V to As^III. Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+ 3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of GST superfamily with arsenic metabolism in a Vietnamese population.