Iodine deficiency is the single most common cause of preventable mental retardation (MR) and brain damage in the world. Iodine deficiency disorders are characterized by MR and the aberrations of T3、T4 and TSH. In China, the Qin-Ba Mountain region (Qinba) is a relatively isolated and traditionally iodine-deficient region with a high prevalence of MR and iodine deficiency diorders (IDD). The etiology of IDD is complex, however, not everyone at risk develops IDD and familial aggregation is common. These suggest that genetic factors may also be involved. In fact, according to the epidemic investigation, the heritability is above 60% either in the non-specific mental retardation of local children or in the pedigree vulnerable to IDD. These data indicates strongly that genetic factors may contribute to iodine deficiency disorder (IDD). Apolipoprotein E (apoE) plays an extensive and central role in lipid metabolism. Several potentially overlapping functions have been ascribed to ApoE, such as lipid transport, neuronal repair, dendritic growth, maintenance of synaptic plasticity and anti-inflammatory activities. Benvenga et al have also demonstrated that the ApoE gene encodes for a lipoprotein possessing a thyroid hormone binding domain in the N-terminal region and that the exon-3 coded region has amino acid sequence homology with regions of the three major thyroid hormone plasma transport proteins (thyroid-binding globulin (TBG), transthyretin (TTR) and albumin) which are known to contain the corresponding hormone binding site(s In addition, the expression of the ApoE gene is controlled at both transcriptional and post-transcriptional loci by the thyroid hormone. Four frequent polymorphisms (?491A/T, ?427T/C , ?219G/T and ε2/3/4, numbered relative to the transcription start site) in the ApoE gene may be in linkage disequilibrium and control the access of transcription factors and the level of transcription of the ApoE gene. After genotyping these four markers, we conducted association study between ApoE and IDD. Singular-locus association analysis between ApoE and intelligence showed that there was no significant difference of frequencies among MR, borderline and control group at any locus of the four SNPs. However, in haplotype analysis, ATTε2, ACGε2, ACGε3 and the global analysis showed positive results. For further analysis, strong positive results were found between the borderline group and controls but not between the MR group and controls. Singular-locus association analysis between ApoE and the metabolic disorders of T3, T4 and TSH revealed that the allelic frequencies of -427T/C and ε2/3/4 were significantly different between cases with the metabolic disorders of T3, T4 and TSH and their matched control group, while the genotype distribution of both the above loci were marginally different. In haplotype analysis, we found that ACGε2 showed positive results using a Fisher exact test. These results are consistent with those of our aboved studies and indicat that ApoE is associated with the metabolic disorders of T3, T4 or TSH, or IDD. We put forward the hypothesis that the influence of ApoE on T3, T4 and TSH may be cumulative and suggest that association studies may be more suitable and more comprehensive if the analysis is based on a metabolic chain, rather than on one individual factor of a metabolic pathway. Taken together, our data provide substantial evidence that ApoE is associated positively with human cogntion and IDD. Paired box gene 8(Pax8)acts as a important regulated transcriptional activator, Pax genes encode a family of transcription factors that are essentially required for the formation of several tissues from all germ layers in the mammalian embryo. Specifically, in organogenesis, they are involved in triggering early events of cell differentiation. In the thyroid gland, PAX8 is essential for the formation of thyroxine-producing follicular cells, which are of endodermal origin. It is sufficient to activate expression of endogenous genes