Polymorphisms in the TSHR (thyrotropin receptor) gene on chromosome 14q31 are not associated with mental retardation in the iodine-deficient areas of China

T W Guo, F C Zhang, J J Gao, L Bian, X C Gao, J Ma, M S Yang, Q Ji, S W Duan, Z J Zheng, R L Li, G Y Feng, D St Clair, L He

Research output: Contribution to journalArticle

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Abstract

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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)179-184
Number of pages6
JournalNeuroscience Letters
Volume382
DOIs
Publication statusPublished - 2005

Keywords

  • TSHR (thyrotropin receptor)
  • mental retardation (MR)
  • thyroid hormone
  • haplotype
  • linkage disequilibrium
  • THYROID-STIMULATING HORMONE
  • MESSENGER-RNA EXPRESSION
  • CONGENITAL HYPOTHYROIDISM
  • DISEASE
  • BRAIN
  • DEIODINASE
  • DISORDER
  • REGION
  • DOMAIN
  • CELLS

Cite this

Polymorphisms in the TSHR (thyrotropin receptor) gene on chromosome 14q31 are not associated with mental retardation in the iodine-deficient areas of China. / Guo, T W ; Zhang, F C ; Gao, J J ; Bian, L ; Gao, X C ; Ma, J ; Yang, M S ; Ji, Q ; Duan, S W ; Zheng, Z J ; Li, R L ; Feng, G Y ; St Clair, D ; He, L .

In: Neuroscience Letters, Vol. 382, 2005, p. 179-184.

Research output: Contribution to journalArticle

Guo, T W ; Zhang, F C ; Gao, J J ; Bian, L ; Gao, X C ; Ma, J ; Yang, M S ; Ji, Q ; Duan, S W ; Zheng, Z J ; Li, R L ; Feng, G Y ; St Clair, D ; He, L . / Polymorphisms in the TSHR (thyrotropin receptor) gene on chromosome 14q31 are not associated with mental retardation in the iodine-deficient areas of China. In: Neuroscience Letters. 2005 ; Vol. 382. pp. 179-184.
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abstract = "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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.",
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author = "Guo, {T W} and Zhang, {F C} and Gao, {J J} and L Bian and Gao, {X C} and J Ma and Yang, {M S} and Q Ji and Duan, {S W} and Zheng, {Z J} and Li, {R L} and Feng, {G Y} and {St Clair}, D and L He",
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T1 - Polymorphisms in the TSHR (thyrotropin receptor) gene on chromosome 14q31 are not associated with mental retardation in the iodine-deficient areas of China

AU - Guo, T W

AU - Zhang, F C

AU - Gao, J J

AU - Bian, L

AU - Gao, X C

AU - Ma, J

AU - Yang, M S

AU - Ji, Q

AU - Duan, S W

AU - Zheng, Z J

AU - Li, R L

AU - Feng, G Y

AU - St Clair, D

AU - He, L

PY - 2005

Y1 - 2005

N2 - 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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

AB - 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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

KW - TSHR (thyrotropin receptor)

KW - mental retardation (MR)

KW - thyroid hormone

KW - haplotype

KW - linkage disequilibrium

KW - THYROID-STIMULATING HORMONE

KW - MESSENGER-RNA EXPRESSION

KW - CONGENITAL HYPOTHYROIDISM

KW - DISEASE

KW - BRAIN

KW - DEIODINASE

KW - DISORDER

KW - REGION

KW - DOMAIN

KW - CELLS

U2 - 10.1016/j.neulet.2005.03.007

DO - 10.1016/j.neulet.2005.03.007

M3 - Article

VL - 382

SP - 179

EP - 184

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

ER -