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, which is located approximately 1 kb upstream of the transcription initiation site associated with promoter B and confers allelic variation of PAX-6 expression in the human brain. In the present association study we tested whether length variation of PAX-6 gene-linked polymorphic region (PAX-6 LPR) influences susceptibility to alcohol dependence.The repeat length of the PAX-6 LPR was assessed in 354 control subjects and 328 alcohol-dependent patients, including four subgroups with a presumed substantial genetic predisposition: (a) with a history of withdrawal complications (n=100); (b) with a history of parental alcoholism (n=115); (c) with early onset (n=67) and (d) with dissocial personality disorders (n=54). Allelic distribution of the PAX-6 LPR did not differ significantly between the controls and the entire group of alcohol-dependent patients χ²=0.015, df 1, p=0.904), or any of the subgroups of patients with severe alcoholism. Our results do not provide evidence that length variation of the PAX-6 LPR contributes to the pathogenesis of alcohol dependence.