The 3′ Part of the Dopamine Transporter Gene DAT1/SLC6A3 Is Associated With Withdrawal Seizures in Patients With Alcohol Dependence
| Autor: | Henri-Jean Aubin, Philip Gorwood, Virginie Burger, Claudette Boni, Jean Adès, Paul Pickering, Nicolas Ramoz, Philippe Batel, Yann Le Strat |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Linkage disequilibrium biology Alcohol dependence Haplotype Confounding Medicine (miscellaneous) Single-nucleotide polymorphism Toxicology Bioinformatics Psychiatry and Mental health Alcohol Withdrawal Seizures biology.protein medicine Allele Psychiatry Psychology Dopamine transporter |
| Zdroj: | Alcoholism: Clinical and Experimental Research. 32:27-35 |
| ISSN: | 0145-6008 |
| Popis: | Background: Some studies have reported that the A9 allele of the variable nucleotide tandemrepeat (VNTR) of the gene which encodes the dopamine transporter (DAT1⁄SLC6A3) is associ-ated with alcoholism withdrawal symptoms such as alcohol withdrawal seizures (WSs), whereasothers did not. We investigated whether polymorphisms within the DAT1 gene are associated withWS taking into account some of the confounding factors such as the severity of alcohol depen-dence.Methods: To further assess the role of this gene in WS, we genotyped the VNTR and 7 singlenucleotide polymorphisms (SNPs) encompassing the DAT1 gene in a sample of 250 alcohol-dependent subjects (175 men and 75 women), of whom 24% exhibited WSs, taking into accountthe severity of alcohol dependence.Results: The VNTR is associated with an increased risk of WSs (odd ratio = 3.5; p = 0.019),even when controlling for confounding factors (p = 0.031). As 2 SNPs, in roughly the same loca-tion of the gene (namely rs27072 and rs27048), are also associated with WSs, it is possible thatthe initial association of the VNTR polymorphism was tagging a specific haplotype of this gene.Indeed, in our sample of alcohol-dependent patients, 2 haplotypes were associated with a signifi-cantly different risk of WSs.Conclusions: The present study adds evidence for a significant role of the 3¢ part of the DAT1gene in WS of alcohol-dependent patients, not only because it is in accordance with previouswork, but also because of larger statistical power (as relying on a sample over sampled with thestudied phenotype), as it gives a more precise analysis of different SNPs within the DAT1 gene,and as it confirms the association when major potentially confounding factors are taken intoaccount in a logistical regression analysis.Key Words: Dopamine Transporter, DAT1⁄SLC6A3, Alcoholism, Withdrawal Seizure, AlcoholDependence. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text