| Background:Parkinson's disease (PD) is one of the most common neurodegenerative disorder, Second only to the incidence of Alzheimer's disease. Major clinical features include bradykinesia, rigidity, resting tremor and postural instability. Pathological features of PD result primarily from loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies. Its cause and pathogenesis has not entirely clear. With the discovery of PD related susceptibility gene, more and more attention is taken to the genetic factors in the pathogenesis of PD. Generally thought that it is the results of the interaction between heredity and environment. However, epidemiological investigation shows that only about5%-10%of patients have genetic factors. Majority of the PD patients is sporadic, and monogenic forms of the disease are rare. Recently, researches on Hypertension, Connective tissue disease. Cancer, proposed that interaction of gene or variants promote the risk of diseases. For different research put forward may have a genetic of PD onset form, gene interaction may exist between each other. The domestic and foreign case report suggests the distribution of genetic mutations in all ethnic groups sporadic Parkinson's disease, and has the area and racial distribution of statistical significance. The genetic mutation carriers in Chinese population have similar reports, but the result is not consistent, shows the genetic mutation genetic heterogeneity special.Recent GWAS have confirmed that some variants in MAPT, LRRK2,SNCA,PARK17,PARK18(HLA-DR)and BST1gene are susceptible factors to PD. PARK16is through the GWS proves to be a PD risk factors in Japan subpopulation in Asia. GBA gene is in almost all people are confirmed for PD risk factors. More recent studies found that some gene sites have interaction. In order to define that alone effect of the PD risk factor and mutual effect alone synergy and accumulative effect among them in Han Chinese, We test the above8gene16polymorphic loci and make multiple genes the correlation analysis.Objective:Through genetype analysis of the Han Chinese's rs823156,rs11240572in PARK16gene, rs11248051,rs1564282in PARK17gene, rs3129882,rs3117098in PARK18gene(HLA-DR gene), rs4698412,rs11931532in BST1gene on the sporadic PD patients and normal controls, combined with the results of analysis for L444P in GBA gene,rs242562,rs2435207in MAPTgene, G2385R,R1628P in LRRK2gene, Rep1,rs11931074,rs356165in SNCA gene in our previous research, and then, through the analysis of the alone efect of the PD risk factor and mutual effect alone synergy and accumulative effect among them in Han Chinese, we discussed that multiple genes may interact with one another.Methods:1) Genes were analysised for,PARK16,PARK17PARK18(HLA-DR) and BST1gene were carried out by polymerase chain reaction (PCR) combined with DNA direct sequencing in1019sporadic PD patients and1030normal controls to discuss the interactions of multiple genes. At the same time,we adopted capillary electrophoresis of SNCA Rep1alleles, with a short tandem repeat sequence analysis technology analysis genotype, final make a polymorphism analysis.2) Using SPSS13.0and Excel2003to do related data processing and statistical analysis, analyse the alone efect of the PD risk factor and mutual effect alone synergy and accumulative effect among SNPs in Han Chinese, Discuss Polygenic determinants association of Parkinson's disease genes.Results:1, rs1564281in PARK17gene, rs4698412in BST1gene were associated with PD with adjustment of sex and age (P<0.05) in the analysis of eight variants.2, rs823156and rs11240572in PARK16gene, rs11248051in PARK17gene, rs3129882and rs3117098in PARK18gene, rs11931532in BST1gene were not associated with PD with adjustment of sex and age (P>0.05) in the analysis of eight variants. 3, Combined with the results of L444P in GBA gene, G2385R in LRRK2gene, Rep1and rs11931074in SNCA gene in previous research, Based on the six sites between multiple factors regression analysis model for polymorphic loci in addition, multiplication interaction analysis. PD risk was increased when Rep1and rs11931074, Repl and G2385R, Repl and rs1564282, Rep1and rs4698412, rs11931074and rsG2385R, rs11931074and rs1564282, rs11931074and rs4698412G2385R and rsl564282, G2385R and rs4698412, rs1564282and rs4698412were combined to association analysis.4, Between the L444P sites in GBA gene and other sites does not exist between synergy.5, On16between sites cohorts function analysis, performance for carrying one respectively site (OR=1.457), two sites (OR=1.750), three sites (OR=3.494) and four sites (OR=23.259), OR value increase gradually. It show that with the increased that carry sites, PD susceptibility increased gradually. Conclusion:1, The rs1564282in PARK17gene and the rs4698412in BST1gene sites changes can increase PD risk.2, G2385R in LRRK2gene, Rep1, rs11931074in SNCA gene, rs1564282in PARK17and rs4698412in BSTl have an independent and combined significant association with PD.3, L444P in GBA gene relative to other sites does not exist interactions, and It may be an independent risk factor.4, Multiple sites may have the accumulation effect, carry the more sites, the greater the risk. |
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