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

Academic Article

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.

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    Keywords

  • Genetics, Interaction, LRRK2, MAPT, Parkinson's disease, SNCA, Adolescent, Adult, Aged, Aged, 80 and over, Asians, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Haplotypes, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Male, Middle Aged, Parkinson Disease, Protein Serine-Threonine Kinases, Risk, Whites, Young Adult, alpha-Synuclein, tau Proteins

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    Author List

  • Heckman MG; Elbaz A; Soto-Ortolaza AI; Serie DJ; Aasly JO; Annesi G; Auburger G; Bacon JA; Boczarska-Jedynak M; Bozi M

    • Start Page

  • 266.e5

    • End Page

  • 266.14

    • Volume

  • 35

    • Issue

  • 1