title: A functional polymorphism in the promoter region of the tryptophan hydroxylase gene is associated with alcohol dependence in one aboriginal group in Taiwan.
abstract: BACKGROUND
  Polymorphisms within intron 7 of the tryptophan hydroxylase (TPH1) gene were found to be associated with alcohol dependence in different ethnic groups, including the aboriginal Bunun group in Taiwan. This study aimed to identify genetic variants at the TPH1 locus and to examine their associations with alcoholism. We hypothesized that the polymorphism of TPH1 gene is functional and influences the human circadian rhythm to contribute to the pathophysiology of alcohol dependence.
  
  
  METHODS
  DNA from the Taiwanese Han and Bunun was subjected to sequence for screening genetic variation in the coding and promoter regions of the TPH1 locus. Polymorphisms among individuals with alcohol dependence and control subjects in two ethnic groups in Taiwan were investigated.
  
  
  RESULTS
  Three variants in the TPH1 promoter region were identified, and the markers are in complete linkage disequilibrium in both populations. Positive associations at both allelic and genotypic levels were obtained between case and control groups in the Bunun. Expression studies demonstrated that the variants indeed affected reporter gene activity in human choriocarcinoma and colon adenocarcinoma cell lines.
  
  
  CONCLUSIONS
  Polymorphisms in the promoter region may influence the function of the TPH1 gene and further influence the proclivity of alcohol dependence in one ethnic group in Taiwan. The associations between TPH1 genotypes and alcoholism may deserve further investigation.
authors.affiliation: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: H Sunny
authors.initials: HS
authors.lastname: Sun
authors.forename: Cathy Shen-Jang
authors.initials: CS
authors.lastname: Fann
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
authors.forename: Yuh-Terng
authors.initials: YT
authors.lastname: Chang
authors.forename: Ching-Jui
authors.initials: CJ
authors.lastname: Chang
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Liu
authors.forename: Andrew Tai-Ann
authors.initials: AT
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013624:Taiwan; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase