<p>Lack of Association Between <em>PLA2G6</em> Genetic Variation and Parkinson’s Disease: A Systematic Review</p>

Abstract

Background: 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 fixedor 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.

Cerebral Iron Deposition in Neurodegeneration

“…Increased alpha-synuclein expression appears to be a direct consequence of iPLA2 deficiency [211]. Yet, several studies examined the association between PLA2G6 genetic variants and PD arriving at the conclusion that monoallelic PLA2G6 variants do not increase PD risk [212][213][214][215]. Patient-derived iPCs with biallelic PLA2G6 mutation differentiated into dopaminergic midbrain neurons exhibited signs of increased endoplasmic reticulum stress.…”

Insights into Lewy body disease from rare neurometabolic disorders

“…There are conflicting reports about the role of variants in PLA2G6 and risk of PD, with some demonstrating an association (Liu et al 2020a , b ) and others not (Liu et al 2020a , b ). However, a study using cells obtained from idiopathic PD patients demonstrated deficient activity of iPLA2, the protein product of PLA2G6 (Zhou et al 2016 ), and it has been reported to be located within Lewy bodies of idiopathic PD cases (Miki et al 2017 ).…”