COMT gene and risk for Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND/AIMS: Several single-nucleotide polymorphisms (SNPs) in the catechol-O-methyltransferase (COMT) gene have been associated with the risk of developing Parkinson's disease (PD). We conducted a systematic review and a meta-analysis including all the studies published on PD risk related with COMT SNPs (mainly rs4680). We also reviewed the possible relationship of COMT SNPs with clinical, neuropharmacological, neurochemical, and neuroimaging features of PD.
MATERIALS AND METHODS: The systematic review was conducted using several databases. Meta-analysis of the eligible studies was carried out using the software Meta-Disc 1.1.1. Heterogeneity between studies was tested using the Q-statistic.
RESULTS: The meta-analysis included 24 association studies for the COMT rs4680 SNP (9719 PD patients, 14 634 controls) and the risk for PD. The frequency of allele positivity showed a significant association between rs4680 and the risk for PD in the total series, as well as homozygosity for the low-activity allele in the Asiatic population (these associations were marginal or disappeared when studies on Hardy-Weinberg disequilibrium were not considered). Global diagnostic odds ratios (95% confidence intervals) for rs4680 were 0.99 (0.94-1.04) for the total group, 0.99 (0.93-1.05) for White, and 1.05 (0.90-1.22) for Asiatic individuals. COMT genotypes could be related with a modest modification in the age at onset of PD, but its possible genotypes in excessive daytime somnolence, impulse control disorders, cognitive impairment, and neuropharmacological or neurochemical variables are unclear.
CONCLUSION: The results of the meta-analysis suggest that the COMT rs4680 polymorphism is not a major determinant of either the risk for PD or clinical, neuropharmacological and neurochemical features of PD. Data on other COMT polymorphisms are scarce but do not suggest association with PD.