Meta-analysis of six genes (BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA) involved in neuroplasticity and the risk for alcohol dependence.

Autor: Forero DA; Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia. Electronic address: diego.forero@uan.edu.co., López-León S; Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA., Shin HD; Laboratory of Genomic Diversity, Department of Life Science, Sogang University, Seoul, Republic of Korea., Park BL; Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, Republic of Korea., Kim DJ; Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Jazyk: angličtina
Zdroj: Drug and alcohol dependence [Drug Alcohol Depend] 2015 Apr 01; Vol. 149, pp. 259-63. Date of Electronic Publication: 2015 Jan 24.
DOI: 10.1016/j.drugalcdep.2015.01.017
Abstrakt: Background: Alcohol-related problems have a large impact on human health, accounting for around 4% of deaths and 4.5% of disability-adjusted life-years around the world. Genetic factors could explain a significant fraction of the risk for alcohol dependence (AD). Recent meta-analyses have found significant pooled odds ratios (ORs) for variants in the ADH1B, ADH1C, DRD2 and HTR2A genes.
Methods: In the present study, we carried out a meta-analysis of common variants in 6 candidate genes involved in neurotransmission and neuroplasticity: BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA. We carried out a systematic search for published association studies that analyzed the genes of interest. Relevant articles were retrieved and demographic and genetic data were extracted. Pooled ORs were calculated using a random-effects model using the Meta-Analyst program. Dominant, recessive and allelic models were tested and analyses were also stratified by ethnicity.
Results: Forty two published studies were included in the current meta-analysis: BDNF-rs6265 (nine studies), DRD1-rs4532 (four studies), DRD3-rs6280 (eleven studies), DRD4-VNTR (seven studies), GRIN2B-rs1806201 (three studies) and MAOA-uVNTR (eight studies). We did not find significant pooled ORs for any of the six genes, under different models and stratifying for ethnicity.
Conclusions: In terms of the number of candidate genes included, this is one of the most comprehensive meta-analyses for genetics of AD. Pooled ORs did not support consistent associations with any of the six candidate genes tested. Future studies of novel genes of functional relevance and meta-analyses of quantitative endophenotypes could identify further susceptibility molecular factors for AD.
(Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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