title: Influence of GSTT1 Genetic Polymorphisms on Arsenic Metabolism.
abstract: A repeated measures study was conducted in Pabna, Bangladesh to investigate factors that influence biomarkers of arsenic exposure. Drinking water arsenic concentrations were measured by inductively-coupled plasma mass spectrometry (ICP-MS) and urinary arsenic species [arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] were detected using High Performance Liquid Chromatography (HPLC) and Hydride Generated Atomic Absorption Spectrometry (HGAAS). Linear mixed effects models with random intercepts were used to evaluate the effects of arsenic contaminated drinking water, genetic polymorphisms in glutathione-S-transferase (GSTT1 and GSTM1) on total urinary arsenic, primary methylation index [MMA/(As3+As5)], secondary methylation index (DMA/MMA), and total methylation index [(MMA+DMA)/(As3+As5)]. Drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and total methylation index. A significant gene-environment interaction was observed between urinary arsenic exposure in drinking water GSTT1 but not GSTM1 where GSTT1nullindividuals had a slightly higher excretion rate of arsenic compared to GSTT1wildtypesafter adjusting for other factors. Additionally, individuals with GSTT1nullgenotypes had a higher primary methylation index and lower secondary methylation index compared to GSTT1wildtypeafter adjusting for other factors. This data suggests that GSTT1 contributes to the observed variability in arsenic metabolism. Since individuals with a higher primary methylation index and lower secondary methylation index are more susceptible to arsenic related disease, these results suggest that GSTT1nullindividuals may be more susceptible to arsenic-related toxicity. No significant associations were observed between GSTM1 and any of the arsenic methylation indices.
authors: Oregon State University, College of Public Health and Human Sciences, Corvallis, OR.
authors: Molly L
authors: ML
authors: Kile
authors: Oregon State University, College of Public Health and Human Sciences, Corvallis, OR.
authors: E Andres
authors: EA
authors: Houseman
authors: Dhaka Community Hospital, 190/1 BaroMoghbazar, Wireless Railgate, 1217, Dhaka, Bangladesh.
authors: Quazi
authors: Q
authors: Quamruzzaman
authors: Dhaka Community Hospital, 190/1 BaroMoghbazar, Wireless Railgate, 1217, Dhaka, Bangladesh.
authors: Mahmuder
authors: M
authors: Rahman
authors: Dhaka Community Hospital, 190/1 BaroMoghbazar, Wireless Railgate, 1217, Dhaka, Bangladesh.
authors: Golam
authors: G
authors: Mahiuddin
authors: Dhaka Community Hospital, 190/1 BaroMoghbazar, Wireless Railgate, 1217, Dhaka, Bangladesh.
authors: Golam
authors: G
authors: Mostofa
authors: Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
authors: Yu-Mei
authors: YM
authors: Hsueh
authors: Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115.
authors: David C
authors: DC
authors: Christiani
keywords: Arsenic; Bangladesh; Environmental health; GSTT1; Gene environment interaction; Methylation; Urinary arsenic