Study On The Association Of Polymorphisms In Nurr1 Gene And Mutations Screening Of PINK1 In Parkinson's Disease

Objective: To determine if there were any associations between the polymorphism (c.-2922(C)2-3, IVS6+18insG) of Nurrrl gene and Parkinson's disease (PD) in a Han population from Sichuan province; to find whether there were any big homozygous deletions or point mutations in the PINK1 gene in early-onset PD and two autosomal recessive Parkinson's disease families.Materials and methods: 1. The association analysis between polymorphisms of Nurr1 and PD were performed using Polymerase chain reaction(PCR), allele-specific PCR (AS-PCR), restriction fragment length polymorphism (RFLP) in a Sichuan han population. 2. PINK1 gene mutations were detected by denaturing high performance liquid chromatography (dHPLC) in 66 early-onset PD and two autosomal recessive Parkinson's disease families. Sequence analysis were used when there were heteroduplex peak.Results: 1. We analysed the two polymorphism sites in 241 PD patients and 236 controls with age, gender, and ethnicity matched. We found no significant differences in allele and genotype frequency of the c.-2922(C)2-3 site in the promoter region between PD and controls (p=0.766). In IVS6+18insG site, the genotypic frequency difference of 3G/3G, 3G/2G and 2G/2G was not statistically significant, but after being stratified by onset age, we found a statistically significant difference between the patients onset age＜50 and controls (χ~2=6.545, p=0.038). The 3G/2G genotypic frequency was higer in PD (onset age＜50) than in controls, and made a statistically significant (χ~2=6.537, p=0.011; OR=1.913, 95% CI 1.159-3.158)。2. We successfully amplificated the whole 8 exons of PINK gene in 66 sporadic PD with onset age＜45 and 22 members from 2 AREP families including 5 patients. No large fragment homozygous deletions and mutation were found.Conclusion: 1. Our study suggests that c.-2922(C)2-3 site in the promoter region is not a risk factor for PD; IVS6+18insG site might be a risk factor for PD with onset age＜50 in our patient group. 2. Our current study haven't found any mutation of PINK1 gene in our patients.