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.
BACKGROUND: Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders, such as depression, anxiety, migraine, substance abuse, and alcoholism. The humanserotonin 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 HTR1BA-161T polymorphism may be valuable both as a functional and as an anonymous genetic marker for HTR1B.
Authors: Lingjun Zuo; Joel Gelernter; Clarence K Zhang; Hongyu Zhao; Lingeng Lu; Henry R Kranzler; Robert T Malison; Chiang-Shan R Li; Fei Wang; Xiang-Yang Zhang; Hong-Wen Deng; John H Krystal; Fengyu Zhang; Xingguang Luo Journal: Neuropsychopharmacology Date: 2011-09-28 Impact factor: 7.853
Authors: Alexis C Edwards; Fazil Aliev; Laura J Bierut; Kathleen K Bucholz; Howard Edenberg; Victor Hesselbrock; John Kramer; Samuel Kuperman; John I Nurnberger; Marc A Schuckit; Bernice Porjesz; Danielle M Dick Journal: Psychiatr Genet Date: 2012-02 Impact factor: 2.458
Authors: Vadim Yuferov; Orna Levran; Dmitri Proudnikov; David A Nielsen; Mary Jeanne Kreek Journal: Ann N Y Acad Sci Date: 2010-02 Impact factor: 5.691
Authors: David Matuskey; Zubin Bhagwagar; Beata Planeta; Brian Pittman; Jean-Dominique Gallezot; Jason Chen; Jane Wanyiri; Soheila Najafzadeh; Jim Ropchan; Paul Geha; Yiyun Huang; Marc N Potenza; Alexander Neumeister; Richard E Carson; Robert T Malison Journal: Biol Psychiatry Date: 2013-11-28 Impact factor: 13.382