Alcohol dehydrogenase alleles in Parkinson's disease

Mutations in alcohol dehydrogenase (ADH; EC 1.1.1.1) genes may be of intere st in the etiology of Parkinson's disease (PD) because of the important rol e these enzymes play in retinoid and dopamine metabolism and/or aldehyde de toxification. The location of several alcohol dehydrogenase genes in a clus ter on chromosome 4 lends further support to ADH genes being candidates for this disorder, because recently a form of autosomal-dominant parkinsonism has been mapped to this area. We sequenced the promoter and coding regions and part of the introns of the human class IV ADH gene in 10 patients with PD. Seven different polymorphisms were identified. These polymorphisms coul d be assigned to four alleles (A1-A4). We then determined the frequencies o f those four alleles and the wild-type allele in 78 patients with PD and 13 0 control subjects and found a significant association of the A1 allele wit h PD (odds ratio = 2.87; 95% confidence interval = 1.35-6.08). In familial cases, the association was strongest (odds ratio = 4.86; 95% confidence int erval = 1.89-12.75). Two patients were homozygous for A1 whereas none of th e 130 control subjects was found to be homozygous. Our results show an asso ciation between a certain ADH4 (formerly known as ADH7 in humans) allele an d PD. This suggests a role for genetic variations of ADH 4 as risk factors for the development of PD. Our data also show that the observed polymorphis ms alone are not sufficient to cause symptoms. Further genetic and/or envir onmental factors have to be involved.