关键词: PRKCG基因, 帕金森病, 单核苷酸多态性, 变性高压液相色谱分析, 病例-对照研究

Abstract: ObjectiveTo screen the variations of the human protein kinase Cγ gene (PRKCG) and study their association with Parkinson's disease(PD).MethodsDNA was extracted from blood of patients with PD and matched normal controls. All 18 exons including the exon-intron junctions were amplified in 17 different PCR fragments, which were analyzed for the presence of variations by DHPLC. The PCR products with a heteroduplex peak were sequenced. Significance was evaluated from 2×2 contingency tables byX² test on the basis of the total number of alleles at each locus. Case-control association analysis was performed between candidate polymorphisms and PD. ResultsIn the 50 early-onset PD(EOPD) patients and 50 controls, there was no missense mutation, insertions or deletions in coding regions of the PRKCG. But 2 different single nucleotide polymorphism(SNPs) in exons, 5 different SNPs and 1 tetranucleotide repeat in introns were identified. Five of them [IVS3+96G>T, IVS11+26T>G, IVS15-41T>C, IVS16-59G>A, IVS16-42(TCTG)_1-2] were described here for the first time. Three of them (IVS11+26T>G, IVS13+76T>C,1497T>C),in complete linkage,constituted a haplotype block. In the preliminary association analysis, the frequency of IVS13+76C, IVS11+26G and 1497C allele on this haplotype block was significantly higher in EOPD patients than the controls (24% vs 9%)(X²=8.165,P=0.004,OR=3.193, 95%CI:1.400-7.282). But in a larger sample of 156 EOPD patients, 153 late-onset PD(LOPD) patients and 195 normal controls, there was no significant difference between the three groups (12.8%,13.7% ,14.6%)(X²=0.471,P=0.790). ConclusionThe PRKCG gene might not be a risk factor for sporadic PD.

Key words: PRKCG, Parkinson's disease, single nucleotide polymorphism, DHPLC, case-control