Family-based Association Study On DIO2 Polymorphism With Mental Retardation In The Population Of QinBa Mountain Area

Mental retardation is a kind of neurological and mental disease with unknown etiology and prevalence incidence of about 1-3% in population. The Qinba mountain region is one of the higher MR prevalence areas in China. The results of the etiology, epidemiology and pedigree's investigation in this region showed that the prevalence of this disease has a character of familial aggregation, which indicates that genetic factors may be one of the important causes leading to MR disorder.Thyroid hormone plays essential roles in metabolism, growth and development, especially in the development of brain nervous system of human. In the fetal period, the deficiency of thyroid hormone may lead to irreversible brain damage and mental retardation. There are many factors influencing the synthesis, transport and function of the thyroid. In particular, the type II deiodinase (DIO2) is one of the most impact factors which can provide adequate active tri-thyroid hormone(T3) for the development of the brain. Therefore, more and more attention focused on the relative study that the iodine-deficiency susceptibility caused by the polymorphisms or abnormality of DIO2 led to mental retardation disease.344 core pedigrees consisting of MR patients and their relatives from the Qinba region of Shaanxi province were studied. Five genetic markers in DIO2 gene were selected and genotyped through PCR-SSCP and PCR-RFLP methods. The reduction and statistical analysis of data were finished using the SPSS package and FBAT5.5 software. The single-marker analysis showed that the allele A of rs2267872 showed an excess transmission from heterozygous parents to affected offsprings in additional model (Z=2.293, P= 0.022) and in dominant model (Z=2.014, P= 0.044). The allele A of rs 1388378 were associated with MR in additional model (Z=2.393, P= 0.017) and in the dominant model (Z=2.756, P= 0.006). The pairwise linkage disequilibrium analysis showed that three SNPs(rs225015,rs225014 and rs225012) and the other two SNPs (rs2267872 and rs1388378) were in strong linkage disequilibrium(D'> 0.8) respectively. The haplotype transmission test revealed that the haplotype GTG of the first three SNPs showed a positive association with MR in additional model(Z=2.226, P= 0.026) and in recessive model(Z=2.651, P= 0.008). The haplotype AA of the last two SNPs showed an excess transmission from heterozygous parents to affected offsprings in additional model(Z=2.241, P= 0.025) and in dominant model(Z=2.073, P= 0.038).In conclusion, the family-based study showed a positive association between DIO2 gene and MR in Chinese Han population of QinBa mountain area. However, more work is needed to further rectify the results in Chinese Han population of other regions.