Polymorphisms in the TSHR (thyrotropin receptor) gene on chromosome 14q31 are not associated with mental retardation in the iodine-deficient areas of China.
Mental retardation (MR) is one of the most frequent handicaps among children. Fetal iodine deficiency disorder (FIDD) is the commonest cause of preventable MR. However, not everyone in the iodine-deficient areas is affected and familial aggregation is common. This suggests that genetic factors may play an important role. Thyroid hormone (TH) plays an important role in fetal and early postnatal brain development. The thyroid-stimulating hormone (TSH, or thyrotropin) receptor (TSHR) is located on the surface of thyroid cells and binds TSH. It results in the production of thyroid hormones via the activation of adenylate cyclase and phospatidylinositol-dependent signaling pathways. Some researchers formulated the hypothesis that TSH receptor expression in the brain may be involved in local thyroid homeostasis through TSH stimulating the DIO2 activity. In the previous study, we have proposed that DIO2 may protect against FIDD in the iodine-deficient areas of China. The TSHR gene, which located on chromosome 14q31 is a potential candidate gene for susceptibility to FIDD. To investigate the potential genetic contribution of TSHR gene, we performed a case-control association study in Chinese Han population from the Qin-Ba mountain regions using four common SNPs in the gene (rs2284716, rs917986, rs2075173 and rs2075179). Pairwise linkage disequilibrium (LD) analysis showed that LD was observed between rs2284716 and rs917986 and between rs2075173 and rs2075179. Single-locus analysis found that all four SNPs in TSHR gene showed no association after correction for multiple testing. Haplotype analysis showed no significant differences in frequency for three sets of haplotypes based on the pariwise LD results. In conclusion, our association results suggest that TSHR gene is not a susceptibility gene for FIDD in the iodine-deficient areas of China.
Guo
Ting-Wei
TW
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China.
Zhang
Fu-Chang
FC
Gao
Jian-Jun
JJ
Bian
Li
L
Gao
Xiao-cai
XC
Ma
Jie
J
Yang
Maosheng
M
Ji
Qian
Q
Duan
Shi-wei
SW
Zheng
Zi-jian
ZJ
Li
Rui-lin
RL
Feng
Guo-yin
GY
St Clair
David
D
He
Lin
L
D000483:Alleles; D002648:Child; D002681:China / Q000453:epidemiology; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D003409:Congenital Hypothyroidism / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007455:Iodine / Q000172:deficiency*; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011989:Receptors, Thyrotropin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011989:Receptors, Thyrotropin; D007455:Iodine