Elsevier

Neuroscience Letters

Volume 276, Issue 2, 3 December 1999, Pages 138-139
Neuroscience Letters

Association analysis of the 5-HT6 receptor polymorphism C267T in Alzheimer's disease

https://doi.org/10.1016/S0304-3940(99)00802-2Get rights and content

Abstract

Serotonergic dysfunction has been implicated in the pathogenesis of Alzheimer's disease (AD). This association study explores whether the serotonin 6 receptor (5-HT6) polymorphism (C267T) is a susceptibility factor for AD. Statistical analysis showed a significant difference in the genotype and gene frequencies between the AD group and the normal controls (P=0.006; and P=0.023, respectively). These findings indicate that the 267C allele of the 5-HT6 gene is a risk factor for AD.

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Acknowledgements

This study is supported by grants from the National Science Committee (NSC88–2314-B-075–064) and National Health Research Institute (DOH-88-HR-604).

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    Vogt et al. (2000) identified six polymorphisms in the gene of 5-HT6 receptor, of which two (a silent 267 C/T in exon 1 (rs 1805054) and a trinucleotide repeat polymorphism ([GCC](2/3)) in the 5′-upstream region of the gene) have been studied more extensively. An association study of these polymorphisms with susceptibility to suicide was negative (Okamura et al., 2005), and a significant association between the 5-HT6 receptor 267 C/T polymorphism with Alzheimer's disease (Tsai, Liu, Liu, Wang, & Hong, 1999) has not been replicated (Thome et al., 2001). Pharmacogenetic studies of the 267 C/T polymorphism and clozapine response in schizophrenia have given contradictory results.

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    Several studies have suggested that it may affect translation through the secondary structure and stability of the mRNA, or be in LD with a functional variant. Therefore, genetic association studies of psychiatric disorders such as schizophrenia (Chiu et al., 2001; Shinkai et al., 1999; Tsai et al., 1999a; Vogt et al., 2000), bipolar disorder (Hong et al., 1999), major depressive disorder (MDD) (Hong et al., 1999) and Alzheimer's disease (Alvarez-Alvarez et al., 2003; Kan et al., 2004; Liu et al., 2001; Tsai et al., 1999b), and pharmacogenic studies of the antipsychotic response in schizophrenia (Ikeda et al., 2008) have so far investigated only rs1805054 in HTR6. However, we found an association of rs6693503 but not rs1805054 (C267T) with METH-induced psychosis patients in this single marker association study.

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    Vogt et al. (2000) identified six polymorphisms in the gene of the 5-HT6 receptor, of which two (a silent 267C/T in exon 1 and a trinucleotide repeat polymorphism ([GCC](2/3)) in the 5′-upstream region of the gene) have been studied more extensively. An association study of these polymorphisms with susceptibility to suicide was negative (Okamura et al., 2005), and a significant association between the 5-HT6 receptor 267C/T polymorphism with Alzheimer's disease (Tsai et al., 1999) has not been replicated (Thome et al., 2001). Pharmacogenetic studies of 267C/T polymorphism and clozapine response in schizophrenia have given contradictory results.

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