title: Association between the 5-HTR1B gene polymorphisms and alcohol dependence in a Han Chinese population.
abstract: The human serotonin receptor 1B (HRT1B) plays an important role in regulating serotonin release. Previous research has suggested that the genetic variation of the HTR1B gene may confer susceptibility to alcoholism or some subtypes of alcohol dependence, but the evidence has been inconsistent. The aim of the present study is to examine whether polymorphic variants of the HTR1B gene are associated with alcohol dependence subtypes or drinking-related behaviors in Chinese Han population. Alcohol-dependent (AD) male patients (n=135) and controls (n=143) were genotyped for two polymorphisms: A161T in the promoter region and the synonymous variation G861C in the coding region of HTR1B. The results showed that the A161T polymorphism was associated with alcohol dependence (T vs. A allele: p=0.002; OR=2.18, 95% CI: 1.32-3.60). This association was strengthened in those with positive family history (OR=3.12, 95% CI: 1.71-5.70) and/or early onset (OR=4.53, 95% CI: 2.18-9.44) of alcohol dependence. The A161T variant was also significantly associated with age of onset of alcoholism (p=0.001). Furthermore, there was a significant difference of haplotypic frequencies between patients and controls (χ(2)=14.84, df=3, p=0.002), with one common haplotype AG of being significantly underrepresented among the patient group compared to the control group (34% vs. 47.7%, permutation p=0.0034; OR=0.56; 95% CI: 0.39-0.79). These findings confirm HTR1B as a susceptibility gene for alcohol dependence in the sample of Chinese Han population. The HTR1B A-161T polymorphism may be particularly valuable as a functional genetic marker for alcoholism and merits additional study.
authors.affiliation: Department of Psychiatry, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Cao
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.forename: Xiang-Mei
authors.initials: XM
authors.lastname: Ye
authors.forename: Yian
authors.initials: Y
authors.lastname: Xia
authors.forename: Colin A
authors.initials: CA
authors.lastname: Haile
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
authors.forename: Xiang Yang
authors.initials: XY
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics*
chemical_list: D015415:Biomarkers; C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B