Association Study Of Gwas-linked Three New Loci In Essential Tremor And Risk Of Sporadic Parkinson's Disease In Chinese Han Population

Background:Parkinson's disease(PD),which is one of the most common movement disorders,has a prevalence of 1.7% after the age of 65 in the Chinese Han Population.The major clinical symptoms of PD are bradykinesia,resting tremor,rigidity,and postural instability.With the aging of the society,the number of PD patients increases year by year,causing serious harm to the health and quality of life of elderly people and bringing heavy financial burden to families and society.The exact etiology of PD remains elusive,although accumulating evidence has demonstrated that genetic factors play an important role in the pathogenesis of the disease.Recently,a genome-wide association study(GWAS)reported that progress has been made in research on gene polymorphism in essential tremor(ET).Five new loci(rs10937625 in STK32 B,rs17590046 in PPARGC1 A,and rs12764057,rs10822974,and rs7903491 in CTNNA3),have been identified,and are significantly associated with increased risk of ET in individuals of Caucasian ancestry.ET and PD have overlapping,potential etiologic and genetic backgrounds,and the GWAS LINGO1 variant has been implicated in etiologic links between ET and PD.Thus,it would be meaningful to explore whether the ET-related genetic variants are also associated with PD.Besides,there is no research on this issue in mainland China.Thus,we conducted this case-control study to verify the relationship between these five polymorphism and sporadic PD in Chinese Han population.Objective:To investigate the polymorphism of STK32 B,PPARGC1A and CTNNA3 genes in Chinese Han population and to analyze whether there is a relationship between the polymorphism of the three loci and the sporadic PD in Chinese Han population.Methods:This is a case-control study and 546 mainland Chinese with sporadic PD and 550 age-and sex-matched healthy individuals were recruited from The First Affiliated Hospital of Zhengzhou University.All patients underwent a standardized neurological examination by two movement disorder specialists,and the diagnosis was made according to the criteria of the United Kingdom PD Society Brain Bank.All subjects were ethnic Hans and gave informed consent.The study received approval from the institutional ethics committee.Genomic DNA was extracted from peripheral blood lymphocytes using standard procedures.We designed specific primers for each single nucleotide polymorphism(SNP)site,and polymerase chain reaction analysis was conducted.Both cases and controls were genotyped by Sanger sequencing.DNASTAR Lasergene MegAlign(v7.1.0)and Chromas(v2.33)were used to conduct sequence alignment.The Hardy-Weinberg equilibrium for genotype-frequency control subjects was examined,and chi-square testing was used to examine the association between the SNPs and PD risk.Result:1.A total of 546 PD patients and 550 healthy controls were included in this study.Statistical analysis showed that there was no statistical difference in gender distribution and age between the two groups(P>0.05).2.In the present study,five polymorphisms of ET-related genes were identified,including rs10937625 of STK32 B,rs17590046 of PPARGC1 A and rs12764057,rs10822974 and rs7903491 of CTNNA3.3.The frequencies of genotypes in the five loci were not statistically significant between the two groups;the additive genetic model,the dominant genetic model and the recessive genetic model had been compared between the two groups,and the results still lacks statistical significance.Conclusion:Our study suggest that essential tremor associated risk loci STK32 B rs10937625,PPARGC1 A rs17590046,CTNNA3 rs12764057,rs10822974,rs7903491 do not play a major role in PD in the Chinese population.