ABSTRACT
OBJECTIVE: To investigate the frequencies of three polymorphisms in DJ-1 (g.168-185del; SNP405, refSNP ID:rs3766606 and 293 G/A) and their association with sporadic Parkinson's disease. METHODS: An association study was performed to determine the genotype of each subject using polymerase chain reaction, restriction fragment length polymorphism and sequence analysis in 192 patients with sporadic Parkinson's disease and 198 healthy controls. RESULTS: In the g.168-185del locus, the Ins/Ins genotype was common and the frequency of Del allele was very low (0.38%). The SNP of 293G/A was not detected in both groups. In the SNP405 G/T site, the GT genotype frequency was significantly higher in patients with age of onset before 40 years than in controls (18.75% vs 5.54%, P=0.004, OR=6.30 95%CI:1.96-20.18). CONCLUSION: The results suggest that the frequencies of the g.168-185del and 293G/A polymorphisms might be different between Chinese and European. The SNP405 GT genotype might be a risk factor for sporadic Parkinson's disease with early age of onset in Sichuan Han population.
Subject(s)
Asian People/genetics , Intracellular Signaling Peptides and Proteins/genetics , Oncogene Proteins/genetics , Parkinson Disease/genetics , Polymorphism, Genetic , Adult , Age of Onset , Aged , Aged, 80 and over , Base Sequence , Case-Control Studies , China , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Parkinson Disease/pathology , Protein Deglycase DJ-1ABSTRACT
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.
