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

Neurobiol Aging. 2021 Jan:97:147.e1-147.e9. doi: 10.1016/j.neurobiolaging.2020.07.004. Epub 2020 Jul 13.

Abstract

This study aimed to evaluate genotype-phenotype correlations of Parkinson's disease (PD) patients with phospholipase A2 group V (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 familial PD and those with sporadic PD. The PLA2G6 variants detected frequently were identified in the early-onset sporadic PD 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 in our cohort, which was considered a risk variant for PD. Thus, the variants of PLA2G6 may play a role in familial PD and early-onset sporadic PD.

Keywords: Genetics; Heterozygote variants; MIBG myocardial scintigraphy; PLA2G6; Parkinson’s disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Cohort Studies
  • Female
  • Gene Frequency / genetics*
  • Genetic Association Studies*
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation*
  • Group VI Phospholipases A2 / genetics*
  • Heterozygote
  • Homozygote
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Parkinson Disease / epidemiology
  • Parkinson Disease / genetics*

Substances

  • Group VI Phospholipases A2
  • PLA2G6 protein, human