Neuropsychopharmacology. 2013 Aug;38(9):1737-47. doi: 10.1038/npp.2013.73. Epub 2013 Mar 21.
Multi-cultural association of the serotonin transporter gene (SLC6A4) with substance use disorder.
Cao J1, Hudziak JJ, Li D.
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Abstract
A
number of studies have reported associations between the serotonin
transporter gene (SLC6A4) and alcohol, heroin, cocaine, or
methamphetamine abuse. Other studies have yielded contrary results.
There are a number of reasons for non-replication, including inadequate
statistical power, population stratification, and poor phenotype
definition. This study was to test the association using a meta-analytic
approach across a variety of racial and ethnic populations. Using the
genotype data of 55 studies (7999 cases, 8264 controls, and 676 families
or parent-offspring trios) published in the past 15 years, we have
conducted comprehensive meta-analyses to examine the associations of the
5-HTTLPR and STin2 polymorphisms with substance use disorder. The
meta-analyses support the associations of 5-HTTLPR with alcohol, heroin,
cocaine, and methamphetamine dependence and abuse (eg, the smallest
P-values were 0.0058 with odds ratio (OR)=0.54 (0.35, 0.84); 0.0024 with
OR=0.77 (0.66, 0.91); 0.018 with OR=1.38 (1.06, 1.81); and 0.028 with
OR=0.46 (0.23, 0.92) for alcohol, heroin, cocaine, and methamphetamine
dependence/abuse, respectively). When all the phenotypes are combined,
the P-value was 0.0006 with OR=0.86 (0.78, 0.94) in the combined
European, Asian, and Mexican populations and P-value was 0.0028 with
OR=1.41 (1.13, 1.78) in the African populations. Evidence of significant
associations was also identified in other subgroup analyses regarding
differently combined substance and populations. The effect sizes of
5-HTTLPR were comparable among the European, Asian, and Mexican
populations, however, the risk allele was more frequent in Asians than
in Europeans and Mexicans. The opposite directions of risk allele in
African population might be driven by the opposite directions of risk
allele in cocaine dependence. This meta-analysis supports that the
association of the SLC6A4 gene with substance use disorder varies
depending on substances with different risk allele frequencies in the
multi-cultural populations. Further studies using larger sample size are
warranted.
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