The Association between Plasma Folate and Selenium Concentrations, Gene Polymorphisms of Selenoprotein and One Carbon Metabolism Related Enzymes and Developmental Delay in Preschool Children

A recent American study reported that the mental retardation and developmental delays (DD) in children was related with the arsenic exposure of mother during pregnancy. Prevalence of DD in 3-5 year-old children increased in Taiwan year by year. Since children with DD require more healthcare services than the general population, raises an important public health issue. Therefore, it is important to explore the etiology of DD in preschool children. Our study showed that urinary total arsenic levels and poor arsenic methylation capacity (high monomethylarsonic acid % (MMAV%) and low dimethylarsinic acid % (DMAV%)) was associated with DD risk. Recently, our study also found that AS3MT gene is associated with DD in preschool children and may partially affect arsenic methylation. However, the mechanism of arsenic methylation capacity related DD is still unclear. Therefore, the aims of this project are to explore the association among plasma selenium and folate concentrations, and polymorphism of selenoprotein (SEPP1 and SEP15), and one carbon metabolism related enzymes- methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and cystathionine-b-synthase (CBS), and DD. In addition, we will explore the interaction of these factors on DD. This project is a two-year prospective study. We will use 179 DD preschool children and their mothers and 88 normal developmental preschool children and their mothers recruited previously in our pilot study from Shin Kong Wu Ho-Su Memorial Teaching Hospital. We carried out the questionnaire interviews and collected their bio-specimens after they provided their written informed consents. The program was approved by the Institutional Review Board of Shin Kong Wu Ho-Su Memorial Teaching Hospital. We determined their urinary arsenic species already. We will continue to recruit 20 DD preschool children and their mothers, and 20 normal developmental preschool children and their mothers in next two each years. First year the plasma selenium, lead and mercury concentrations and the polymorphisms of selenoprotein SEPP1 (rs3797310) and SEP15 (rs5859) will be examined; we also determine urinary arsenic species of new study subjects. Second year, we will continue to examine plasma selenium, lead and mercury concentrations and polymorphisms of selenoprotein and urinary arsenic species of new study subjects, and measure plasma folate concentrations and polymorphisms of one carbon metabolism related enzymes- MTHFR (C677T and A1298C), MTR (rs1801394) and CBS (rs234709 and rs4920037). This study will use external environmental exposure dose, internal dose and susceptibility genes to perform molecular epidemiology of DD in preschool children. To examine plasma selenium and folate concentrations and polymorphisms of SEPP1, SEP15, MTHFR, MTR, and CBS on DD risk in preschool children after adjustment for plasma lead and mercury and urinary arsenic levels, and other risk factors. Finally, we will incorporate all data to perform statistical analyses. We anticipate setting up and evaluating the interaction of these factors on DD risk in preschool children. We expect to understand a part of mechanisms on DD in preschool children. The findings from these two years projects are expected to publish in internationally prestigious journals.