Association Between Polymorphisms Of NLRP3 Gene And Parkinson's Disease In Northern Chinese Han Population

Objective:Studies have found that innate immune and inflammatory responses play a vital role in the pathogenesis of Parkinson's disease(PD).Nucleotide-binding domain-like receptor protein 3(NLRP3)inflammatory bodies are the most common and most studied inflammatory bodies.NLRP3-mediated neuroinflammation can cause mesencephalic dopamine neuron degeneration.Plays a key role.Histological studies found that NLRP3expression was elevated in midbrain neurons of PD patients.We hypothesized that the NLRP3 gene polymorphism may be related to the risk of PD.The study aimed to investigate the association between NLRP3(rs10754558,rs4612666,and rs7525979)gene polymorphisms and Parkinson's disease susceptibility in the Northern Han Chinese population.Methods:A case-control study was performed in 400 patients with PD and 400 healthy age and sex-matched individuals,Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)was used to detect two NLRP3 polymorphisms(rs10754558,rs4612666 and rs7525979).SPSS 21.0 statistical software was used for statistical analysis.Measurement data were analyzed by two independent samples t-test.Numeration data were analyzed by X~2 test.The correlation between NLRP3 and PD was analyzed using Logistic regression.The relative risk was expressed as odds ratio(OR)and 95%confidence interval(CI).The P<0.05 indicates that the difference is statistically significant.Results:For the rs4612666,the alleles T and C in the PD group were significantly different from the control group(P=0.021).The frequency of the C allele was lower in the PD group(47%)than in the control group(52.8%),the difference between the two groups is statistically significant,which may reduce the risk of PD(OR 0.794,95%CI 0.653-0.967,P=0.021).Rs4612666 carriers of CC genotype have a lower risk of developing PD than carriers of TT genotype(p=0.019).The recessive genetic model CC/TT+CT distribution was statistically significant between the PD group and the control group.Compared with TT+CT genotype carriers,CC genotype carriers had a lower risk of PD(OR 0.667,95%CI 0.481-0.925,P=0.015).In the subgroup analysis,adjusted age factors,female PD group allele distribution and allele frequency distribution were significantly different from the control group(p=0.003,p=0.018).In addition,the female PD C allele frequency was significantly lower than in the control group(OR 0.644,95%CI 0.481-0.863,p=0.003).After adjusting for gender factors,the allele frequency of early-onset PD was significantly different from that of the control group,and the allele of early-onset PD C was significantly lower than that of the control group(OR 0.636,95%CI 0.437-0.926,p=0.018).Under the analysis of recessive genetic pattern,compared with the control group,female PD and early-onset PD were significantly different(p=0.002,p=0.013).However,the genotype distribution and allele frequency of rs10754558 and rs7525979 loci were not statistically different between the PD group and the control group(P>0.05).This study failed to find strong linkage disequilibrium and there was no statistical significance between the PD group and the control group.there were no significant differences between the two genetic models.Further,we did not observe linkage disequilibrium(LD)in the three NLRP3polymorphismsConclusion:The NLRP3 gene polymorphism might be related to the risk of developing PD in Northern Chinese Han population and the mutants of NLRP3 rs4612666polymorphism may be a protective factor against PD in the Han population in northern China.In the subgroup analysis,it can be found that rs4612666 is associated with the risk of female PD and early-onset PD.The C allele Carriers of rs4612666 may reduce the risk of incidence of females and early-onset Han Chinese in northern China.