Association analysis of a PAX-6 gene promoter-associated polymorphic repeat with alcohol dependence

The human paired box-containing gene PAX-6 participates in the development and plasticity of the brain including the limbic system, the neural system that plays a crucial role in reward processes. We have reported recently a polymorphic dinucleotide repeat sequence with the structure (AC)m(AG)n, whi ch is located similar to 1 Kb upstream of the transcription initiation site associated with promoter B and confers allelic variation of PAX-6 expressi on in the human brain. In the present association study we tested whether l ength variation of PAX-6 gene-linked polymorphic region (PAX-6LPR) influenc es susceptibility to alcohol dependence. The repeat length of the PAX-6LPR was assessed in 354 control subjects and 328 alcohol-dependent patients, in cluding four subgroups with a presumed substantial genetic predisposition: (a) with a history of withdrawal complications (n = 100); (b) with a histor y of parental alcoholism (n = 115); (c) with early onset (n = 67) and (d) w ith dissocial personality disorders (n = 54). Allelic distribution of the P AX-6LPR did not differ significantly between the controls and the entire gr oup of alcohol-dependent patients (chi(2) = 0.015, df 1, p = 0.904), or any of the subgroups of patients with severe alcoholism. Our results do not pr ovide evidence that length variation of the PAX-6LPR contributes to the pat hogenesis of alcohol dependence.