HEREDITARY VARIATIONS IN MONOAMINE-OXIDASE AS A RISK FACTOR FOR PARKINSONS-DISEASE

Parkinson's disease (PD) is a common neurodegenerative disorder caused by loss of dopaminergic neurons in the brainstem. Recent studies sugg est that several genes may have a role in determining individual susce ptibility to this disease, and the degradative enzyme monoamine oxidas e (MAO) has been implicated in the disease process. Wide differences i n activity levels for both forms of this enzyme (MAO-A and MAO-B) exis t in the human population, and levels of both are genetically determin ed. Here we have compared the frequency of haplotypes at the MAOA and MAOB loci an the X chromosome in 91 male patients with PD and 129 male controls. Alleles were marked using two restriction fragment length p olymorphisms (RFLPs), a (GT)n repeat in the MAOA locus, and a (GT)n re peat in the MAOB locus. One particular haplotype marked by the RFLP's at MAOA was three times more frequent in patients with PD as compared with controls, and the overall distribution of these alleles was signi ficantly different (p = 0.03) between these two groups. Another MAOA h aplotype was about threefold more common in controls than in patients with PD (p = 0.005). No associations were observed between individual MAOB alleles and the disease state, but the frequency distribution for all alleles was significantly different in the two populations (p = 0 .046). These findings support the idea that the MAO genes may be among the hereditary factors that influence susceptibility of individuals t o PD.