Association Between CD36 Gene Polymorphisms And Susceptibilities To Sporadic Parkinson’s Disease In Northern Chinese Han Population

Objective: Accumulating evidence has demonstrated that neuroinflammation is involved in the pathogenesis of Parkinson’s disease(PD),leading to irreversible and progressive loss of dopaminergic neurons.CD36,a class B scavenger receptor,mediates the microglial uptake of aggregated α-synuclein,leading to the activation of the Nod-like receptor protein3(NLRP3)inflammasome and the secretion of proinflammatory cytokines interleukin(IL)-1β,and inducing persistent neuroinflammation.Recent whole-exome sequencing study has suggested that the CD36 is associated with sporadic PD in Caucasian population.However,the association between CD36 gene polymorphisms and sporadic PD susceptibility in northern Chinese Han population has not yet been studied.Therefore,this study aimed to evaluate whether CD36 rs1761667,rs1049673,and rs1527479 single-nucleotide polymorphisms are associated with sporadic PD susceptibility in northern Chinese Han population.Methods: We recruited 864 northern Han Chinese subjects without consanguinity,including 403 PD patients and 461 healthy controls,in this case-control study.Peripheral venous blood was collected for DNA extraction,and CD36 rs1761667,rs1049673,and rs1527479 polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).All statistical analyses were performed using IBM SPSS Statistics,version 25.0.The distributions of allele and genotype frequencies between PD patients and healthy controls were compared using the chi-square test.Odds ratios(OR)and 95% confidence intervals(95% CI)were calculated to evaluate the relationship between the SNPs of the CD36 gene and PD risk using logistic regression analysis.Results: There were statistically significant differences in rs1761667 in the genotype frequencies(AA vs.GG,OR = 1.629,95% CI= 1.045–2.539,P = 0.031)and recessive models(AA vs GG+GA,OR = 1.517,95% CI= 1.004-2.291,P = 0.048),which indicated that the rs1761667 AA genotype was related to an increased risk of PD.Further subgroup analyses indicated that the A allele of rs1761667 was associated with a higher prevalence of late-onset PD(LOPD)and male PD(P=0.016 and P=0.011,respectively).The frequency of the AA genotype for rs1761667 was higher in male patients with PD(P = 0.025)and LOPD(P = 0.033)than in healthy controls,indicating that the rs1761667 AA genotype and A allele were associated with LOPD and male PD susceptibility.However,there was no significant association between the rs1049673 and rs1527479 polymorphisms and sporadic PD in either whole or subgroup analyses.Eight haplotypes were detected,and the ACC,ACG,GCC,ATG,and GCG haplotypes were associated with PD susceptibility.Conclusion: Our results indicate that CD36 rs1761667 polymorphism was associated with sporadic PD susceptibility in northern Chinese Han population.The rs1761667 AA genotype was related to an increased risk of PD.The AA genotype and A allele of rs1761667 may be risk factors for LOPD and male PD.CD36 rs1761667 polymorphism has potential for clinical application as a biomarker to determine susceptibility to sporadic PD.