Association Between Epidermal Growth Factor Receptor Gene Polymorphisms And Susceptibility To Parkinson’s Disease

Objective: The progressive loss of dopaminergic neurons in the mesencephalic substantia nigra is recognized as an important pathological feature of Parkinson’s disease(PD).Several research studies have suggested that the epidermal growth factor receptor(EGFR)signaling pathway may play a significant role in the survival and functional development of dopaminergic neurons.Therefore,genetic variations in these pathways may be related with PD susceptibility.The aim of our study was to explore the association between selected single nucleotide polymorphisms(SNPs)of the EGFR gene,including rs730437,rs3752651 and rs11506105,and susceptibility to Parkinson’s disease in a Han Chinese population.Methods: A total of 870 Han Chinese subjects,including 435 PD patients and 435 healthy controls,were enrolled in this case-control study.Peripheral blood was obtained from all subjects for DNA extraction,and selected SNPs(rs730437,rs3752651,rs11506105)of the EGFR gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The allele and genotype frequencies were calculated through direct count,and the differences in the frequencies of genotype and allele gene polymorphisms between patients with PD and healthy controls were analyzed using the Chi-square test,P values that were less than 0.05 were considered to indicate statistical significance.Logistic regression analysis was applied for calculating the odds ratios(ORs)and 95% confidence intervals(CIs)to evaluate potential associations.Results: We found that the genotype distributions of rs730437 and rs11506105 polymorphisms showed significant differences between the PD and control groups.Compared with healthy control subjects,the frequencies of the AC genotype and C allele of rs730437 were significantly lower in PD patients,although statistical significance was low(for AC genotype,OR=0.742,95%CI=0.553-0.996,P=0.047;for C allele,OR=0.756,95%CI=0.599-0.954,P=0.018).In the dominant model,the CC+AC genotype showed a lower frequency,compared with the AA genotype(OR=0.726,95%CI=0.549-0.958,P=0.024),which demonstrated that it was related with a decreased risk of PD.After multiple group comparisons based on gender and age of onset,these differences in genotype and allele frequencies were still found in EOPD patients,compared with matched control subjects(P=0.024 for genotype,P=0.005 for allele).Concerning the rs11506105 polymorphism,the comparison between the GG genotype and G allele indicated statistical significance,with lower prevalence in PD patients than healthy controls(for GG genotype,OR=0.438,95%CI=0.290-0.915,P=0.028;for G allele,OR=0.778,95%CI=0.617-0.981,P=0.034).When considering the recessive model,the frequency of GG genotype,compared with the sum of frequencies of the A genotype under heterozygosity or homozygosity were significantly lower in patients with PD,compared with healthy controls(OR=0.465,95%CI=0.224-0.965,P=0.036).The subgroup analysis,which included comparisons based on age and gender,showed lower frequencies of the genotype and allele in female patients suffering from PD,compared with matched healthy female controls(P=0.024 for genotype,P=0.007 for allele;Table 5).No significant difference in rs3752651 polymorphism was observed between the PD group and the control group.In addition,when the whole series was tested using subgroup analyses,based on age and gender,the genotypes and allele frequencies of rs3752651 showed few differences with no statistical significance between patients suffering from PD and healthy controls.Furthermore,we detected seven common haplotypes between PD patients and controls in this population,while the AAT haplotype was found to be related with PD susceptibility with statistical significance(P=0.0088).Conclusion: Our study demonstrated the significant correlation found between EGFR genetic variation and sporadic PD,female PD and EOPD in the Han Chinese population.Furthermore,the C allele of rs730437 and the G allele of rs11506105 may be protective factors against the pathogenesis of PD.These EGFR polymorphisms may be potential diagnostic biomarkers of PD.Considering the limitations of this study,detailed investigations using larger sample sizes of different racial populations are warranted to further analyze the association between the EGFR gene and PD.