LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case-control association study for Parkinson's disease

Mol Genet Genomic Med. 2019 Nov;7(11):e604. doi: 10.1002/mgg3.604. Epub 2019 Sep 5.

Abstract

Background: The LRRK2 gene is associated with Parkinson's disease (PD) as a number of mutations within the gene have been shown to be susceptibility factors. Studies on various global populations have determined that mutations such as G2019S, G2385R, and R1628P in LRRK2 increase the risk of developing PD while the N551K-R1398H haplotype is associated with conferring protection against developing PD. Here we report a study looking at the N551K and R1398H variants for the first time in the Malaysian population.

Methods: Cases (523) which conformed to the United Kingdom PD Brain Bank Criteria for PD were recruited through trained neurologists and age- and ethnically matched controls (491) were individuals free of any neurological disorder. The N551K and R1398H mutations were genotyped using the Taqman SNP genotyping assay.

Results: A significant protective association for N551K was found in those of Malay ancestry, with a protective trend seen for R1398H. A meta-analysis of Chinese individuals in this cohort with other published cohorts of Chinese ancestry indicated a significant protective role for N551K and R1398H.

Conclusion: This study reports that the N551K-R1398H haplotype is also relevant to the Malaysian population, with a significant protective effect found in those of Malay and Chinese ancestries.

Keywords: LRRK2; N551K; Parkinson's disease; R1398H.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics*
  • Malaysia / epidemiology
  • Male
  • Middle Aged
  • Mutation*
  • Parkinson Disease / epidemiology
  • Parkinson Disease / genetics*
  • Prognosis

Substances

  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2