Association Of PPAR? Gene Polymorphisms With Sporadic Parkinson's Disease In A Northern Chinese Population

Objective:Previous studies have shown that peroxisome proliferator-activated receptor?agonists have protective effects on Parkinson's disease(PD).This study aimed to assess the association between PPAR?gene polymorphism and susceptibility to Parkinson's disease(PD)in a northern Chinese population.Methods:391 Chinese Han PD patients(female 185,male 206)who met the British brain bank criteria for Parkinson's disease were selected and enrolled into the PD group.391 healthy subjects(female 178,male 213)who matched the age and gender of PD group were enrolled into the control group.All peripheral venous blood samples were collected and DNA was extracted for cryopreservation.All subjects genotype on PPAR? gene in rs3856806,rs1801282,-1279G/A were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)analysis and gene sequencing.PD patients were divided into different subgroups according to age(?50 years old;>50 years old)and sex:early onset PD group,late onset PD group,male PD group and female PD group.The differences in allele type distribution and allele frequency between PD group and control group,PD subgroups and control group,and PD subgroups were compared.rs3856806 and-1279G/A were analyzed by additive,dominant and recessive gene models respectively.Haploview software was used to analyze the haplotype and linkage disequilibrium of rs3856806,rs1801282 and-1279 G/A.Results:The results showed that there was no significant difference in genotype distribution of the three loci between PD group and control group(P>0.05);There was no significant difference in gene frequency between the two groups for rs3856806 and rs1801282(P>0.05);The frequency of allele A in PD group was higher than that in control group(P=0.037,OR=1.639,95%CI=1.027-2.616).The PD group and the control group were compared under different genetic models:for rs3856806 locus,no significant difference was found in the analysis of the three genetic models;For the-1279G/A locus,analysis in additive model(AG vs.GG:P=0.019,OR=1.837,95%CI=1.104-3.057)and dominant model(AG+AA vs.GG:P=0.024,OR=1.768,95%CI=1.078-2.898)showed that the locus may be correlated with Parkinson's disease.Subgroup analysis:for rs3856806 genetic polymorphism,after stratified analysis of onset age and sex,there was no statistical difference between the groups;For rs1801282 genetic polymorphism,the genotype distribution was statistically different between early-onset PD group vs.control group,early-onset PD group vs.late-onset PD group(P=0.005;p=0.008),and G allele frequency in early-onset PD group was significantly higher than that in control group and late-onset PD group(P=0.006,OR=3.093,95%CI=1.446-6.615;P=0.009,OR=2.899,95%CI=1.344-6.253);For the-1279G/A genetic polymorphism,the genotype distribution was statistically different between the early-onset PD group and the control group(P=0.02),the frequency of allele A in early-onset PD group was significantly higher than that in control group(P=0.019,OR=2.667,95%CI=1.263-5.629),while in male PD group it was higher than that in male control group(P=0.032,OR=1.998,95%CI=1.051-3.798).The haplotype distribution of rs3856806,rs1801282 and-1279G/A showed no statistical difference between the two groups(P>0.05),and there was no strong linkage disequilibrium(-1279 G/A and rs1801282:D=0.749,r~2=0.427;-1279G/A,rs3856806:D'=0.678,r~2=0.087;rs1801282 and rs3856806,D'=0.595,r~2=0.051).Conclusions:The study showed that in a northern Chinese population,the A allele of-1279G/A might be a risk factor for PD and the G alle of rs1801282 might increase the susceptibility of EOPD.This may provide new ideas for future PD prediction and treatment.