Mutation screening and association analysis of the parkin gene in Parkinson's disease patients from South-West China.

Various deletions and point mutations in the Parkin gene have been strongly associated with Parkinson's disease (PD) and parkinsonism, especially when the onset occurs at a young age. In this study, we screened 25 "early-onset" (<49 years at onset) and 91 later-onset PD patients from a Han Chinese population from South-West China for deletions and mutations in the Parkin gene. We found no deletions or point mutations in exons 1-12 of the Parkin gene using direct sequence analysis and only detected the common Ser167Asn polymorphism. We analysed Ser167Asn in 116 patients with sporadic PD and 124 controls, matched for age and gender. There were significant differences in allele and genotype frequency between PD patients, with the 167Asn allele more common in cases than controls (46.6 vs. 35.1%; chi(2) = 6.54, p = 0.011, odds ratio = 1.61, 95% confidence interval, CI, 1.10-2.37), as was the 167Asn genotype (17.3 vs. 11.3%; p = 0.04). The frequency of the 167Ser genotype was significantly lower in PD patients than in controls when compared with that of the other two genotypes combined (chi(2) = 7.84, p = 0.005, odds ratio = 0.46, 95% CI 0.25 - 0.82). No significant differences in the frequencies of the allele and genotypes were found between patients classified into two groups according to symptoms at onset (chi(2) = 0.191, p = 0.66, odds ratio = 1.12, 95% CI 0.65-1.95; chi(2) = 0.24, p = 0.887) or age of onset (p = 0.787). In summary, homozygous deletion mutations and point mutations in exons 1-12 of the Parkin gene were not detected in this Han Chinese population, although we cannot exclude compound heterozygous deletions. In addition, our study suggests that the variant 167Asn increases the risk of developing PD. Copyright 2003 S. Karger AG, Basel