Genetic analysis of Parkin in early onset Parkinson's disease (PD): Novel intron 9 g > a single nucleotide polymorphism and risk of Taiwanese PD

Early onset Parkinson's disease (PD) has been associated with mutations in Parkin. We screened Parkin mutations in a cohort of Taiwanese early onset PD using direct cDNA sequencing. Two deletions (Ex2-3del and Ex5del), one point mutation (R334C), one 86-bp IVS9 insertion (c.1084intron⁺), and two polymorphisms (S167N and V380L) were identified. The mutations identified are heterozygous and none of the mutation carriers possess two Parkin mutations. The c.1084intron⁺ was due to a novel IVS9 g>a change. To assess the association of IVS9 g>a, S167N and V380L with the risk of PD, we conducted a case - control study in a cohort of PD and ethnically matched controls. Although the difference is not significant, the V380L C allele frequency was notably lower inPDpatients than the controls and a trend toward decrease in risk of developing PD was evident (odds ratio: 0.71, 95% confidence interval: 0.53-0.97, P=0.029). Contrarily the IVS9 g>a a allele frequency was notably higher in PD patients than the controls and a trend toward increase in risk of developing PD was also evident (odds ratio: 1.65, 95% confidence interval: 1.06-2.59, P=0.028). Quantitative real-time PCR showed that the relative Parkin c.1084intron⁺ mRNA expression was increased in PD patients with IVS9 ga genotype as compared to gg genotype. Pairwise genotype analysis revealed that IVS9 gg genotype strengthens the negative association of the V380L GC genotype with PD (odds ratio: 0.67, 95% confidence interval: 0.48-0.94, P=0.021). The results of Parkin mutation/ polymorphism screening may contribute to our understanding of PD.