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Association study of novel human serotonin 5-HT(1B) polymorphisms with alcohol dependence in Taiwanese Han
Hsiao Fang Sunny Sun1, Yuh Terng Chang, Cathy Shen-Jang Fann
1Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan.
Background:
Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders, such as depression, anxiety, migraine, substance abuse, and alcoholism. The human serotonin receptor 1B, encoded by the HTR1B gene, is a presynaptic serotonin autoreceptor that plays a role in regulating serotonin synthesis and release. Because the linkage of antisocial alcoholism to the HTR1B gene was recently reported in two populations, it was of interest to identify genetic variants at the HTR1B locus and study their association with alcoholism in the Taiwanese Han population.
Methods:
We sequenced DNA from Taiwanese Han to screen for genetic variation in the coding, promoter, and partial 3' untranslated regions of the HTR1B locus of 158 alcohol-dependent cases with withdrawal symptoms and 149 control subjects, who either never drank or drank only occasionally and in low quantities.
Results:
Seven variants were identified. Positive associations were found between variant A-161T and alcohol dependence at both the allelic and genotypic level. In addition, an expression study showed that the A-161T variant affected reporter gene activity.
Conclusions:
Our results support an association between HTR1B and alcohol dependence. The HTR1B A-161T polymorphism may be valuable both as a functional and as an anonymous genetic marker for HTR1B.