A different genetic background is postulated for alcoholics with early onset and with antisocial personality disorder (type 2 alcoholics) compared with those with late onset and without antisocial personality disorder (type 1 alcoholics). The dopamine transporter (DAT) and the serotonin transporter (SERT) are involved in endophenotypes that are associated with these subtypes.
Our study was aimed at investigating whether distinct haplotypes, defined by polymorphisms associated with the expressions of DAT and SERT, were associated with subgroups of alcohol dependence.
Intron 8 variable number of tandem repeats (VNTR), exon 15 rs27072 and VNTR (DAT), promoter VNTR and rs25531, and intron 2 VNTR (SERT) were genotyped in a case-control sample comprising 360 alcoholics and 368 controls, and in a family-based sample of 65 trios, all of German origin.
DAT: The haplogenotypes 6-A-10/6-G-10 and 5-G-9/5-G-9 were more often present in type 2 alcoholics as compared with type 1 alcoholics [odds ratio (OR): 2.8], and controls (OR: 5.8), respectively. The daily ethanol consumption was associated with haplogenotypes.
SERT: haplotypes SA-10 (OR: 2.3) and LG-12 (OR: 2.5) were more often present in type 2 alcoholics compared with controls. Haplotype LA-10 was less often present in type 2 alcoholics (OR: 0.5), and was more often transmitted, in families, to the affected offspring (transmission disequilibrium test: OR: 5.2; family-based association test: Z: 1.9).
The haplotype LA-12 was significantly undertransmitted to affected offspring in the whole group (transmission disequilibrium test: OR: 0.216; family-based association test: Z: -2.2).
A gene by environment interaction was observed with respect to the time course of the depression score after alcohol withdrawal and with respect to the positive family history of alcohol dependence.
Haplotype analysis, sub-grouping with respect to more homogeneous endophenotypes, and inclusion of quantifiable characteristics are sensible strategies to untangle the genetic background of such a complex disorder like alcohol dependence.
Request Reprint E-Mail: adrian.kraschewski@charite.de
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