An association study between the transthyretin (TTR) gene and mental retardation

J Li, J J Gao, F C Zhang, Q H Xing, F L Dang, X C Gao, S W Duan, Z J Zheng, X Q Qian, W Qin, X W Li, Y F Han, J Li, G Y Feng, David Malcolm St Clair, L He

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Abstract

It is known that in the pathogenesis of mental retardation (MR), both genetic and environmental factors (particularly iodine deficiency) appear to play a critical role. Transthyretin (TTR) transports between 20% and 30% of serum thyroxine in normal individuals and it is the main T-4-binding protein in CSF. Variability in the TTR gene may influence risk for iodine-deficiency-based MR. The SNPs we selected from dbSNP were detected and identified using ARMS-PCR and sequencing methods, and we identified five novel sequence variants. Singular-locus association analysis indicated no association between the TTR gene and MR. In haplotype analysis, however, we found a haplotype CGTG+ (rs723744/G+6649C/T+6690C/rs2276382/del9) showed a weak positive association with MR (chi(2) = 6.699, p = 0.035). Finally, we concluded that the weak positive result is more likely to be due to sampling error and the small size of this haplotype resulting from its relative low frequency. Our negative results provide no evidence that variants of TTR gene influence susceptibility to MR in the iodine-deficient areas of China and suggest that there may be a compensatory mechanism(s) in humans and mice, which work(s) to compensate the effect of mutation in the TTR gene on MR.

Original languageEnglish
Pages (from-to)230-235
Number of pages6
JournalEuropean Archives of Psychiatry and Clinical Neuroscience
Volume256
Issue number4
Early online date19 Dec 2005
DOIs
Publication statusPublished - 2006

Keywords

  • transthyretin (TTR) gene
  • mental retardation
  • polymorphism
  • haplotype
  • familial amyloidotic polyneuropathy
  • thyroid hormone
  • transport protein
  • hyperthyroxinemia
  • prealbumin
  • thyroxine
  • mutation
  • iodine
  • brain
  • mouse

Cite this

An association study between the transthyretin (TTR) gene and mental retardation. / Li, J ; Gao, J J ; Zhang, F C ; Xing, Q H ; Dang, F L ; Gao, X C ; Duan, S W ; Zheng, Z J ; Qian, X Q ; Qin, W ; Li, X W ; Han, Y F ; Li, J ; Feng, G Y ; St Clair, David Malcolm; He, L .

In: European Archives of Psychiatry and Clinical Neuroscience, Vol. 256, No. 4, 2006, p. 230-235.

Research output: Contribution to journalArticle

Li, J, Gao, JJ, Zhang, FC, Xing, QH, Dang, FL, Gao, XC, Duan, SW, Zheng, ZJ, Qian, XQ, Qin, W, Li, XW, Han, YF, Li, J, Feng, GY, St Clair, DM & He, L 2006, 'An association study between the transthyretin (TTR) gene and mental retardation', European Archives of Psychiatry and Clinical Neuroscience, vol. 256, no. 4, pp. 230-235. https://doi.org/10.1007/s00406-005-0630-6
Li, J ; Gao, J J ; Zhang, F C ; Xing, Q H ; Dang, F L ; Gao, X C ; Duan, S W ; Zheng, Z J ; Qian, X Q ; Qin, W ; Li, X W ; Han, Y F ; Li, J ; Feng, G Y ; St Clair, David Malcolm ; He, L . / An association study between the transthyretin (TTR) gene and mental retardation. In: European Archives of Psychiatry and Clinical Neuroscience. 2006 ; Vol. 256, No. 4. pp. 230-235.
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T1 - An association study between the transthyretin (TTR) gene and mental retardation

AU - Li, J

AU - Gao, J J

AU - Zhang, F C

AU - Xing, Q H

AU - Dang, F L

AU - Gao, X C

AU - Duan, S W

AU - Zheng, Z J

AU - Qian, X Q

AU - Qin, W

AU - Li, X W

AU - Han, Y F

AU - Li, J

AU - Feng, G Y

AU - St Clair, David Malcolm

AU - He, L

PY - 2006

Y1 - 2006

N2 - It is known that in the pathogenesis of mental retardation (MR), both genetic and environmental factors (particularly iodine deficiency) appear to play a critical role. Transthyretin (TTR) transports between 20% and 30% of serum thyroxine in normal individuals and it is the main T-4-binding protein in CSF. Variability in the TTR gene may influence risk for iodine-deficiency-based MR. The SNPs we selected from dbSNP were detected and identified using ARMS-PCR and sequencing methods, and we identified five novel sequence variants. Singular-locus association analysis indicated no association between the TTR gene and MR. In haplotype analysis, however, we found a haplotype CGTG+ (rs723744/G+6649C/T+6690C/rs2276382/del9) showed a weak positive association with MR (chi(2) = 6.699, p = 0.035). Finally, we concluded that the weak positive result is more likely to be due to sampling error and the small size of this haplotype resulting from its relative low frequency. Our negative results provide no evidence that variants of TTR gene influence susceptibility to MR in the iodine-deficient areas of China and suggest that there may be a compensatory mechanism(s) in humans and mice, which work(s) to compensate the effect of mutation in the TTR gene on MR.

AB - It is known that in the pathogenesis of mental retardation (MR), both genetic and environmental factors (particularly iodine deficiency) appear to play a critical role. Transthyretin (TTR) transports between 20% and 30% of serum thyroxine in normal individuals and it is the main T-4-binding protein in CSF. Variability in the TTR gene may influence risk for iodine-deficiency-based MR. The SNPs we selected from dbSNP were detected and identified using ARMS-PCR and sequencing methods, and we identified five novel sequence variants. Singular-locus association analysis indicated no association between the TTR gene and MR. In haplotype analysis, however, we found a haplotype CGTG+ (rs723744/G+6649C/T+6690C/rs2276382/del9) showed a weak positive association with MR (chi(2) = 6.699, p = 0.035). Finally, we concluded that the weak positive result is more likely to be due to sampling error and the small size of this haplotype resulting from its relative low frequency. Our negative results provide no evidence that variants of TTR gene influence susceptibility to MR in the iodine-deficient areas of China and suggest that there may be a compensatory mechanism(s) in humans and mice, which work(s) to compensate the effect of mutation in the TTR gene on MR.

KW - transthyretin (TTR) gene

KW - mental retardation

KW - polymorphism

KW - haplotype

KW - familial amyloidotic polyneuropathy

KW - thyroid hormone

KW - transport protein

KW - hyperthyroxinemia

KW - prealbumin

KW - thyroxine

KW - mutation

KW - iodine

KW - brain

KW - mouse

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DO - 10.1007/s00406-005-0630-6

M3 - Article

VL - 256

SP - 230

EP - 235

JO - European Archives of Psychiatry and Clinical Neuroscience

JF - European Archives of Psychiatry and Clinical Neuroscience

SN - 0940-1334

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ER -