Protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

The best validated susceptibility variants for Parkinson's disease are located in the α-synuclein (SNCA) and microtubule-associated protein tau (MAPT) genes. Recently, a protective p.N551K-R1398H-K1423K haplotype in the leucine-rich repeat kinase 2 (LRRK2) gene was identified, with p.R1398H appearing to be the most likely functional variant. To date, the consistency of the protective effect of LRRK2 p.R1398H across MAPT and SNCA variant genotypes has not been assessed. To address this, we examined 4 SNCA variants (rs181489, rs356219, rs11931074, and rs2583988), the MAPT H1-haplotype-defining variant rs1052553, and LRRK2 p.R1398H (rs7133914) in Caucasian (n = 10,322) and Asian (n = 2289) series. There was no evidence of an interaction of LRRK2 p.R1398H with MAPT or SNCA variants (all p ≥ 0.10); the protective effect of p.R1398H was observed at similar magnitude across MAPT and SNCA genotypes, and the risk effects of MAPT and SNCA variants were observed consistently for LRRK2 p.R1398H genotypes. Our results indicate that the association of LRRK2 p.R1398H with Parkinson's disease is independent of SNCA and MAPT variants, and vice versa, in Caucasian and Asian populations.

Detaljer

Författare
  • Michael G. Heckman
  • Alexis Elbaz
  • Alexandra I. Soto-Ortolaza
  • Daniel J Serie
  • Jan O. Aasly
  • Grazia Annesi
  • Georg Auburger
  • Justin A. Bacon
  • Magdalena Boczarska-Jedynak
  • Maria Bozi
  • Laura Brighina
  • Marie-Christine Chartier-Harlin
  • Efthimios Dardiotis
  • Alain Destée
  • Carlo Ferrarese
  • Alessandro Ferraris
  • Brian Fiske
  • Suzana Gispert
  • Georgios M. Hadjigeorgiou
  • Nobutaka Hattori
  • John P A Ioannidis
  • Barbara Jasinska-Myga
  • Beom S. Jeon
  • Yun Joong Kim
  • Christine Klein
  • Rejko Kruger
  • Elli Kyratzi
  • Chin-Hsien Lin
  • Katja Lohmann
  • Marie-Anne Loriot
  • Timothy Lynch
  • George D. Mellick
  • Eugénie Mutez
  • Grzegorz Opala
  • Sung-Sup Park
  • Simona Petrucci
  • Aldo Quattrone
  • Manu Sharma
  • Peter A. Silburn
  • Young Ho Sohn
  • Leonidas Stefanis
  • Vera Tadic
  • Hiroyuki Tomiyama
  • Ryan J. Uitti
  • Enza Maria Valente
  • Demetrios K. Vassilatis
  • Carles Vilariño-Güell
  • Linda R. White
  • Karin Wirdefeldt
  • Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium
Enheter & grupper
Externa organisationer
  • Skåne University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik

Nyckelord

Originalspråkengelska
Sidor (från-till)266.e5-266.e14
TidskriftNeurobiology of Aging
Volym35
Utgåva nummer1
StatusPublished - 2014 jan
PublikationskategoriForskning
Peer review utfördJa