Lack of association between the LRRK2 A419V variant and Asian Parkinson's disease

Ann Acad Med Singap. 2013 May;42(5):237-40.

Abstract

Introduction: The G2385R and R1628P LRRK2 gene variants have been associated with an increased risk of Parkinson's disease (PD) in the Asian population. Recently, a new LRRK2 gene variant, A419V, was reported to be a third risk variant for PD in Asian patients. Our objective was to investigate this finding in our cohort of Asian subjects.

Materials and methods: Eight hundred and twenty-eight subjects (404 PD patients, and 424 age and gender-matched control subjects without neurological disorders) were recruited. Genotyping was done by Taqman® allelic discrimination assay on an Applied Biosystems 7500 Fast Real-Time PCR machine.

Results: The heterozygous A419V genotype was found in only 1 patient with PD, compared to 3 in the control group (0.4% vs 1.3%), giving an odds ratio of 0.35 (95% confidence interval (CI), 0.01 to 3.79; P = 0.624).

Conclusion: A419V is not an important LRRK2 risk variant in our Asian cohort of patients with PD. Our data are further supported by a literature review which showed that 4 out of 6 published studies reported a negative association of this variant in PD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine / genetics*
  • Case-Control Studies
  • China / ethnology
  • Cohort Studies
  • Cytosine
  • Female
  • Gene Frequency
  • Genetic Variation / genetics*
  • Genotype
  • Heterozygote
  • Humans
  • India / ethnology
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Malaysia / ethnology
  • Male
  • Middle Aged
  • Parkinson Disease / genetics*
  • Polymorphism, Genetic / genetics
  • Protein Serine-Threonine Kinases / genetics*
  • Risk Factors
  • Singapore
  • Thymine
  • Valine / genetics*
  • Young Adult

Substances

  • Cytosine
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases
  • Valine
  • Alanine
  • Thymine