title: Association Study of Gene Polymorphisms in GABA, Serotonin, Dopamine, and Alcohol Metabolism Pathways with Alcohol Dependence in Taiwanese Han Men.
abstract: BACKGROUND
  The roles of GABA, serotonin, dopamine, and alcohol metabolism pathways in alcohol dependence (AD) are evident from animal models and human studies. Aims of this study were to investigate associations between genes in the 4 pathways and AD.
  
  
  METHODS
  Male subjects from 2 independent samples of Taiwanese Han descent, a family sample of 179 trios and a case-control sample of 262 AD cases and 273 normal controls, were included in this study. The Schedules for Clinical Assessment in Neuropsychiatry was used for phenotype assessment of AD. We genotyped 282 single nucleotide polymorphisms (SNPs) located in 61 candidate genes involving alcohol metabolism, serotonin, and GABA systems among the family sample and replicated the top hits in the case-control sample.
  
  
  RESULTS
  Fifteen SNPs located in 10 genes showed signals of associations (FBAT test p < 0.05) with AD in the family sample. Three SNPs, rs1229984 in ADH1B, rs671 in ALDH2, and rs2000292 in HTR1B, were significantly replicated in the case-control sample (p = 5.87 × 10(-14) , 5.12 × 10(-14) , and 0.0051, respectively). In the combined meta-analysis, these 3 SNPs and 1 additional SNP, rs698 in ADH1C, showed significant association after correcting for multiple comparisons, and rs1229984 and rs671 showed the strongest association (p < 10(-16) ). Logistic regression conditioning on rs1229984 and rs671 in the case-control sample showed that rs2000292 in HTR1B remained nominally significant.
  
  
  CONCLUSIONS
  Genes in alcohol metabolism pathway, especially ADH1B and ALDH2, conferred the major genetic risk for AD in Taiwanese Han population. Some genes in GABA and serotonin pathways showed nominal association with AD.
authors: Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
authors: Lawrence Shih-Hsin
authors: LS
authors: Wu
authors: Department of Medicine, MacKay Medical College, Taipei, Taiwan.|Department of Psychiatry, Mackay Memorial Hospital, Taipei, Taiwan.
authors: Chau-Shoun
authors: CS
authors: Lee
authors: Department of Computer Sciences and Engineering, Yuan Ze University, Taoyuan, Taiwan.
authors: Tzu-Ya
authors: TY
authors: Weng
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Kathy Hsiao-Tsz
authors: KH
authors: Wang
authors: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors: Andrew Tai-Ann
authors: AT
authors: Cheng
mesh_terms: D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000502:physiology; D000437:Alcoholism / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000502:physiology; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D016022:Case-Control Studies; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000502:physiology; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D013624:Taiwan; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D012701:Serotonin; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D004298:Dopamine
keywords: Alcohol Dependence; Alcohol-Metabolizing Enzymes; Dopamine; GABA; Serotonin