文摘
The best validated susceptibility variants for Parkinson's disease are located in the ¦Á-synuclein (m>SNCAm>) and microtubule-associated protein tau (m>MAPTm>) genes. Recently, a protective p.N551K-R1398H-K1423K haplotype in the leucine-rich repeat kinase 2 (m>LRRK2)m> 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 m>MAPTm> and m>SNCAm> variant genotypes has not been assessed. To address this, we examined 4 m>SNCAm> variants (rs181489, rs356219, rs11931074, and rs2583988), the m>MAPTm> 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 m>MAPTm> or m>SNCAm> variants (all m>pm> ¡Ý 0.10); the protective effect of p.R1398H was observed at similar magnitude across m>MAPTm> and m>SNCAm> genotypes, and the risk effects of m>MAPTm> and m>SNCAm> 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 m>SNCAm> and m>MAPTm> variants, and vice versa, in Caucasian and Asian populations.