Objective: A recent large-scale meta-analysis of genome-wide association data in Europe has identified and replicated 28 loci for Parkinson’s disease (PD) including 6 new risk loci(SIPA1L2, INPP5F, MIR4697, GCH1, VPS13C and DDRGK1). Considering the population-specific heterogeneity, independent replication is needed to confirm genetic association from the specific population. Therefore, we conducted a case-control study to examine the genetic associations of VPS13C rs2414739, MIR4697 rs329648, GCH1 rs11158026 and SIPA1L2 rs10797576 with PD in 2137 Han Chinese subjects from mainland People’s Republic of China.

Background: Genome-wide association studies (GWAS) have shed light on the genetic basis of PD, with the identification and replication of risk loci. To date, many GWAS of PD and GWAS meta-analysis in Caucasian, Europe and Asian populations have been published and identified nearly 30 PD genetic loci including some novel PD genetic loci.

Methods: We examined genetic associations of VPS13C rs2414739, MIR4697 rs329648, GCH1 rs11158026 and SIPA1L2 rs10797576 with PD susceptibility in a Han Chinese population of 1028 sporadic PD patients and 1109 healthy controls. We also conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus.

Results: In this study, no significant differences were observed in the minor allele frequency (MAF) among cases and controls at the four loci. Subjects of GCH1 rs11158026 with CC+CT genotypes had an increased risk compared to those with TT genotype among the younger age group (<50 years of age,OR=1.411, 95% CI=1.042, 1.911, P = 0.026). For the other three loci, we did not observe any significant difference in genotype distribution between PD patients and controls. Besides, minor allele carriers cannot be distinguished from non-carriers based on their clinical features at the four loci.

Conclusions: Our study provides strong support for the susceptibility role of GCH1 rs11158026 in sporadic PD in a Han Chinese population from mainland People’s Republic of China, but we are unable to demonstrate the association between VPS13C rs2414739, MIR4697 rs329648 and SIPA1L2 rs10797576 and PD susceptibility. Additional replication studies in other populations and functional studies are warranted to better validate the role of the four new loci in PD risk.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-of-four-new-candidate-genetic-variants-with-parkinsons-disease-in-han-chinese/