Association Analysis Of Five Susceptibility Genes And Sporadic Parkinson’s Disease In Chinese Han Population

Background:The mechanism of Parkinson’s disease (PD) is still not very clear, but genetics play more and more important role in the development of PD. So far, GWAS of Parkinson’s disease in various populations have found dozens of susceptibility genes associated with PD. Two large meta-analysis including five GWAS in the USA and Europe population have identified several novel PD suscepitibility locus (rsl2456492in RIT2, rs708723in RAB7L1, rs156429in GPNMB, rs6812193in STBD1and rs34016896in NMD3). As far as now, those loci are still unknown in a Han Chinese population from mainland China, and the underlying relationship between those genes and cognitive impairment of PD and dyskinesia needs further research.Objective:To investigate the association between suscepitibility locis (rsl2456492in RIT2, rs708723in RAB7L1, rs156429in GPNMB, rs6812193in STBD1and rs34016896in NMD3) and sporadic PD in Chinese Han population. Moreover, to explore the relationship between those suscepitibility genes and cognitive impairment and dyskinesia in PD.Methods:Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) assay was used to detect the suscepitibility locus (rsl2456492in RIT2, rs708723in RAB7L1, rs156429in GPNMB, rs6812193in STBD1and rs34016896in NMD3) in460sporadic PD and476healthy controls. Meanwhile, we genotype analysis of those locus in PD-NC patients, PD-MCI patients and PD-D patients. Additionaly, we carried out an association analysis in PD with LID and PD without LID.Results:1. There was statistical difference in allele and genotype frequencies of RIT2gene rsl2456492between SPD patient group and healthy control group (allele G:P=0.007, OR=1.296, genotype GG:P=0.008, OR=1.284).2. Significant difference was revealed in allele and genotype distribution of RAB7L1gene rs708723between SPD patient group and healthy control group (allele C:P=0.010, OR=0.783, genotype CC:P=0.011, OR=0.782).3. There is no statistical difference in allele or genotype frequencies of rs156429in GPNMB between SPD patient group and healthy control group, but significant difference was obsevered between male patients and healthy control group (allele G:P=0.014, OR=0.673, genotype GG: P=0.012, OR=0.654).4. No statistically significant difference in both genotype and allele distribution between PD and control for rs6812193in STBD1and rs34016896in NMD3.5. There are statistical differences in allele and genotype frequencies of rs12456492in RIT2between PD-MCI plus PD-D group and PD-NC group (allele G:P=0.032, OR=1.523, genotype GG:P=0.040, OR=1.480).6. Strong evidence of an association for rs34016896in NMD3was observed in autosomal recessive inheritance models between PD with LID group and PD without LID group (P=0.009, OR=3.688).Conclusion:1. RIT2rs12456492polymorphism is a risk factor of PD. RAB7L1rs708723polymorphism can decrease the risk of PD, but GPNMB rs156429polymorphism can only reduce the risk of male PD patients. STBD1rs6812193polymorphism and NMD3rs34016896polymorphism are not related to PD in Chinese population.2. RIT2gene rs12456492. polymorphism is associated with cognitive impairment in PD patient.3. NMD3gene rs34016896polymorphism may be associated with dyskinesia in PD patient.