Lack of Association Between PLA2G6 Genetic Variation and Parkinson’s Disease: A Systematic Review

Hongmei Liu,1– 3,* Yamin Yao,1,3,* Hongbo Liu,4,* Yanmin Peng,1,3,* Juanjuan Ren,2,3 Xiaohui Wu,1,3 Ruizhi Mao,1,3 Jie Zhao,1,3 Yuncheng Zhu,1,3 Zhiang Niu,1,3 Tao Yang,1,3 Xiujia Sun,2,3 Ping Jiang,2,3 Chen Zhang,1– 3 Yiru Fang1– 3,5 1Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Laboratory of Biochemistry and Pharmacology, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Blood Transfusion, Loudi Center Hospital, Loudi, People’s Republic of China; 5CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiru Fang; Chen Zhang Email yirufang@aliyun.com; zhangchen645@163.comBackground: The phospholipase A2 Group 6 (PLA2G6, also known as PLA2, PARK14, and iPLA2) gene encodes a group VIA calcium-independent phospholipase A2. Genetic polymorphism of PLA2G6 has been indicated to be involved in conferring susceptibility for Parkinson’s disease (PD), whereas conclusive results have not been obtained. Thus, we intended to conduct a systematic review to determine if PLA2G6 genetic variation confers a greater susceptibility to PD.Methods: All case-control studies that investigated the association of the PLA2G6 polymorphisms with the risk of PD published before 15 July 2018 were included. The literature was comprehensively searched and identified in five English databases (EBSCO, Pubmed, OVID, EMBASE and ISI Web of Knowledge) and four Chinese databases (Wanfang database, Chinese Biomedical Literature Database, China Academic Journals Database and VIP database). We performed analyses of study characteristics, heterogeneity, and forest plot in analyses analogous to dominant, codominant and additive models with the pooled odds ratio (OR) in fixed- or random-effects models as the measure of association.Results: A total of 664 potentially relevant studies were retrieved with the initial search, of which eight studies fulfilled the inclusion criteria, and included 2,779 PD patients and 3,291 control participants,. Among all the reported 27 genetic variants, 15 single nucleotide polymorphisms (SNPs) were present only in patients, and only five available SNPs (rs2267369, rs140758033, c.1959T>A (Gly653Gly), rs76718524, rs199935023) were pooled in the meta-analysis. However, there was no evidence for a significant association between the five SNPs and PD risk in dominant, codominant and allele models, suggesting a lack of association between PLA2G6 genetic variation and PD susceptibility.Conclusion: The present study assessed the association of PLA2G6 genetic polymorphism with the risk PD, and the result strongly demonstrates that PLA2G6 polymorphism is not associated with PD susceptibility.Keywords: Parkinson’s disease, PD, PLA2G6, systematic review