title: Meta-Analysis Reveals Significant Association of the 3'-UTR VNTR in SLC6A3 with Alcohol Dependence.
abstract: Although many studies have analyzed the association of 3'-untranslated region variable-number tandem repeat (VNTR) polymorphism in SLC6A3 with alcohol dependence (AD), the results remain controversial. This study aimed to determine whether this variant indeed has any genetic effect on AD by integrating 17 reported studies with 5,929 participants included.
  
  
  
  The A9-dominant genetic model that considers A9-repeat and non-A9 repeat as 2 genotypes and compared their frequencies in alcoholics with that in controls was adopted. Considering the potential influence of ethnicity, differences in diagnostic criteria of AD, and alcoholic subgroups, stratified meta-analyses were conducted. There existed no evidence for the presence of heterogeneity among the studied samples, indicating the results under the fixed-effects model are acceptable.
  
  
  
  We found a significant association of VNTR A9 genotypes with AD in all ethnic populations (pooled odds ratio [OR] 1.12; 95% confidence interval [CI] 1.00, 1.25; p = 0.045) and the Caucasian population (pooled OR 1.15; 95% CI 1.01, 1.31; p = 0.036). We also found VNTR A9 genotypes to be significantly associated with alcoholism as defined by the DSM-IV criteria (pooled OR 1.18; 95% CI 1.03, 1.36; p = 0.02). Further, we found a significant association between VNTR A9 genotypes and alcoholism associated with alcohol withdrawal seizure or delirium tremens (pooled OR 1.55; 95% CI 1.24, 1.92; p = 1.0 × 10(-4) ). In all these meta-analyses, no evidence of publication bias was detected.
  
  
  
  We concluded that the VNTR polymorphism has an important role in the etiology of AD, and individuals with at least 1 A9 allele are more likely to be dependent on alcohol than persons carrying the non-A9 allele.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China.|Center for Air Pollution and Health, Zhejiang University, Hangzhou, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China.|Center for Air Pollution and Health, Zhejiang University, Hangzhou, China.
authors.forename: Rongli
authors.initials: R
authors.lastname: Fan
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China.|Center for Air Pollution and Health, Zhejiang University, Hangzhou, China.|Institute for NeuroImmune Pharmacology, Seton Hall University, South Orange, New Jersey.
authors.forename: Ming D
authors.initials: MD
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D018598:Minisatellite Repeats / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human
keywords: 3′-UTR VNTR; Alcohol Dependence; Alcoholism; Meta-Analysis; Polymorphism; SLC6A3