The Studies Of Mutations And Polymorphism On PINK1 Gene Of Patients With Parkinson Disease In Guangxi

Objective: To study deletion mutations,point mutations and polymorphism of PINK1 gene exons 1 to 8 in the GuangXi patients with Parkinson disease. To analyze the association between these changes with the etiology in the disease.Methods: PINK1 gene's all exons of 50 Parkinson patients (28 early - onset Parkinson patients and 22late-onset Parkinson patients )and 55 controls (17 you- ng controls and 38 old controls )were amplified by polymerase chain reaction (PCR).The PCR particulartic production and their deletion mutations were dete- cted by agarose gel electrophoresis. Point mutations of the exons were identified by single strand conformation polymorphism (SSCP). And in the samples with abnormal SSCP results, were performed by sequencing analyze to confirm the mutations,polymorphism types and theirs locations. If polymorphism types were found by sequencing analyze,the polymorphism types of other members would be detected by dot blotting, radiant developing. Allele and genotype frequencies werecompared by the Chi-square test.Results: We found no deletion mutation of the exons in all the patients and the controls. However, a knowned heterozygosis point mutation G12169A in exon 5 was identified in 1 patients of early-onset Parkinson Disease. This mutat- eon led a change that a isoleucine took the place of methionine in the protein. And we found that G12164A polymerphism and the intronic IVS5-5G-A (G12101A)polymorphism were located on PINK1 gene of exon 5.They are chain relation,that isn't reported beford. There were G/G and G/A genotypes in G12164A polymorphism,none is A/A geno type , There were G/A and A/A genotypes in IVS5-5G -A(G12101A)polymorphism,none is G/G genotype. G12164A substitution led a change that a threonine took the place of arginine in the protein. Bioinformatic analysis showed that the intronic IVS5-5G-A(G1210 1A) polymorphism was located within acceptor site of exon 5 and may be the functional single polymorphhism in the regulatory region impacting on the splic- ing of PINK1 gene .The chain relation polymorphism G/A,A/A genotypes frequ- ency was significantly higher in PD group(42%) than the Control (23.6%) (X2= 4.034, P = 0.045 ). The frequency was also significantly higher in late-onset Parkinson patients (45.5%) than the old control (21.1%) ( X2 = 3.951, P=0.047 ) There were no significant differences in alleles.Conclusions: Our finding suggests that the deletion mutation and Point mutation are rare of PD patients in Guangxi. Chain relation polymorphism at G12164A and IVS5-5G -A (G12101A)in PINK1gene might be a susceptible factor for PD patients.