A study of five candidate genes in Parkinson's disease and related neurodegenerative disorders

Objective: To determine whether reported genetic association of polymorphis ms in the CYP2D6, CYP1A1, N-acetyltransferase 2 (NAT2), DAT1, and glutathio ne s-transferase M1 (GSTM1) genes with PD were evident in a population of 1 76 unrelated patients with sporadic PD and to extend these findings to othe r disease groups (familial PD [n = 30], ALS [n = 50], multiple system atrop hy [n = 38], progressive supranuclear palsy [n = 35], and AD [n = 23]). Met hods: A combination of allele-specific PCR and analysis of restriction frag ment length polymorphisms were performed. Results: We genotyped 1,131 indiv iduals. After matching each patient with a control subject by age, sex, eth nicity, and geographic origin, there was no association of any allele/genot ype with any of the six disease groups. There was an increased frequency of NAT2 slow acetylators in the ALS group compared with controls (70% versus 50%; OR 2.33 [95% CI, 1.03 to 5.30]), but this was not significant after ad justing for multiple testing. Conclusions: This is one of the most extensiv e candidate gene studies performed in PD and the first time that some of th ese loci have been studied in multiple system atrophy and progressive supra nuclear palsy. In contrast with previous studies, we found no role for thes e polymorphisms in the etiology of PD, ALS, multiple system atrophy, progre ssive supranuclear palsy, or AD.