The Deiodinase Type 2 (DIO2) Gene and Mental Retardation in Iodine Deficiency

This chapter investigates the potential genetic contribution of deiodinase type 2 (DIO2), performing a case-control association study using three common SNPs in the gene (rs225014, rs225012, and rs225010) that were in strong linkage disequilibrium with each other. Thyroid hormone (TH) plays an important role in fetal and early postnatal brain development. The pro-hormone T4 is converted in the brain to its active form, T3, or its inactive metabolite; reverse T3, mainly by the action of DIO2. MR is a disability characterized by significant limitations both in intellectual functioning and in adaptive behavior. The disability is often congenital and present at birth, but by definition must be present before age 18. A case-control association study using SNPs in the DIO2 gene was performed and DIO2 was found to be associated with MR in iodine-deficient areas. The normal DIO2 enzyme activity, especially local enzyme activity in the brain, may be an important protection factor of brain development from the late first trimester and early second trimester of gestation. It can be concluded that allelic variation in the DIO2 gene may affect the amount of T3 available and, in an iodine-deficient environment, partly determine the overall risk of MR. The results suggested that DIO2 enzyme activity, especially local enzyme activity in the brain, may have an important contribution to brain development.