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Evaluation of four candidate genes encoding proteins of the dopamine pathway in familial and sporadic Parkinson's disease

We assessed the role of four candidate genes encoding proteins involved in dopaminergic transmission, the dopamine transporter (DAT), the dopamine receptor D2 (DRDB), and the main catabolic enzymes of dopamine, monoamine oxidase A (MAOA) and B (MAOB), through allelic association studies in a population of familial and sporadic Parkinson's disease (PD). Using intronic polymorphisms of the four candidate genes, we studied the allelic distributions of the polymorphic markers in 18 affected members, one patient was chosen randomly from each PD family; 60 sporadic PD and 60 healthy unrelated control subjects were matched for sex and for country of origin. All subjects were white. To complete the study of the DRD2, we subsequently tested 40 additional sporadic PD and 40 control patients, who were recruited using a similar procedure. For DAT, MAOA, MAOB polymorphisms, similar allelic frequencies were present in familial, sporadic PD and control patients. In contrast, at the DRD2 locus, the overall allelic distribution was significantly different in the sporadic PD (p < 0.01) and in the familial PD groups (p < 0.05), each was compared with the controls. The odd ratios were significant (p < 0.01) in sporadic PD and in familial PD for allele 3 with respective values of 1.84 (95% CI, 1.23–2.74) and 2.83 (95% CI, 1.32–6.08). Individuals who were homozygous for allele 3 were 2.3 times more frequent in the sporadic PD than in controls. Results suggest that DRD2, but not DAT, MAOA and MAOB, might be a genetic determinant of PD in the population tested.