PLA2G6 variants associated with the number of affected alleles in Parkinson’s disease in Japan

Abstract The phospholipase A2 group VI (PLA2G6) gene plays a role in familial Parkinson’s disease (fPD). This study aimed to evaluate the allele frequency and genotype-phenotype correlations of patients with PLA2G6 variants. We analyzed the DNA of 798 patients with PD, including 78 PD patients reported previously, and 336 in-house controls. We screened the exons and exon-intron boundaries of PLA2G6 using the ion Torrent system and Sanger method. We identified 21 patients with 18 rare variants, such that 1, 9, and 11 patients were homozygous, heterozygous, and compound heterozygous, respectively, with respect to PLA2G6 variants. The allele frequency was approximately equal between patients with fPD and those with sporadic PD (sPD). The PLA2G6 variants were detected frequently were identified in the early-onset sPD group. Patients who were homozygous for a variant showed more severe symptoms than those who were heterozygous for the variant. The most common variant was p.R635Q, which was detected more frequently in our patients than in the controls in a public database. The p.R635Q variant was considered a risk variant for PD. Thus, the variants of PLA2G6 may play a role in fPD and early-onset sPD.