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Meta‐Analysis Reveals Significant Association of the 3′‐ UTR VNTR in SLC 6A3 with Alcohol Dependence
Author(s) -
Ma Yunlong,
Fan Rongli,
Li Ming D.
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13104
Subject(s) - odds ratio , confidence interval , meta analysis , variable number tandem repeat , genotype , delirium tremens , allele , medicine , genetics , biology , psychiatry , gene
Background Although many studies have analyzed the association of 3′‐untranslated region variable‐number tandem repeat ( VNTR ) polymorphism in SLC 6A3 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. Methods 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. Results 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. Conclusions 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.