Protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants.
Protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent of MAPT and SNCA variants.
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DOI：
10.1016/j.neurobiolaging.2013.07.013
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发表时间：
2014-01
影响因子：
4.2
通讯作者：
Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium
中科院分区：
文献类型：
--
作者：
Heckman MG;Elbaz A;Soto-Ortolaza AI;Serie DJ;Aasly JO;Annesi G;Auburger G;Bacon JA;Boczarska-Jedynak M;Bozi M;Brighina L;Chartier-Harlin MC;Dardiotis E;Destée A;Ferrarese C;Ferraris A;Fiske B;Gispert S;Hadjigeorgiou GM;Hattori N;Ioannidis JP;Jasinska-Myga B;Jeon BS;Kim YJ;Klein C;Kruger R;Kyratzi E;Lin CH;Lohmann K;Loriot MA;Lynch T;Mellick GD;Mutez E;Opala G;Park SS;Petrucci S;Quattrone A;Sharma M;Silburn PA;Sohn YH;Stefanis L;Tadic V;Tomiyama H;Uitti RJ;Valente EM;Vassilatis DK;Vilariño-Güell C;White LR;Wirdefeldt K;Wszolek ZK;Wu RM;Xiromerisiou G;Maraganore DM;Farrer MJ;Ross OA;Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium
经过验证的帕金森病 (PD) 易感性变异最好位于 α-突触核蛋白 (SNCA) 和微管相关蛋白 tau (MAPT) 基因中。最近，在富含亮氨酸重复激酶 2 (LRRK2) 基因中发现了一种保护性 p.N551K-R1398H-K1423K 单倍型，其中 p.R1398H 似乎是最有可能的功能变体。迄今为止，尚未评估 LRRK2 p.R1398H 对 MAPT 和 SNCA 变异基因型的保护作用的一致性。为了解决这个问题，我们检查了白种人 (N=10,322) 和亚洲人中的四个 SNCA 变体 (rs181489、rs356219、rs11931074、rs2583988)、MAPT H1 单倍型定义变体 rs1052553 和 LRRK2 p.R1398H (rs7133914) (N=2,289) 系列。没有证据表明 LRRK2 p.R1398H 与 MAPT 或 SNCA 变异存在相互作用（所有 P≥0.10）；在 MAPT 和 SNCA 基因型中观察到 p.R1398H 的保护作用具有相似的程度，并且对于 LRRK2 p.R1398H 基因型观察到 MAPT 和 SNCA 变体的风险影响一致。我们的结果表明，在白种人和亚洲人群中，LRRK2 p.R1398H 与 PD 的关联独立于 SNCA 和 MAPT 变异，反之亦然。
The best validated susceptibility variants for Parkinson’s disease (PD) are located in the alpha-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 four SNCA variants (rs181489, rs356219, rs11931074, rs2583988), the MAPT H1-haplotype defining variant rs1052553, and LRRK2 p.R1398H (rs7133914) in Caucasian (N=10,322) and Asian (N=2,289) 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 PD is independent of SNCA and MAPT variants, and vice versa, in Caucasian and Asian populations.
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影响因子：
11.2
作者：
Goris, An;Williams-Gray, Caroline H.;Sawcer, Stephen J.
通讯作者：
Sawcer, Stephen J.
影响因子：
2.5
作者：
Evans, W;Fung, HC;Hardy, J
通讯作者：
Hardy, J
影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
9.9
作者：
Bower, JH;Maraganore, DM;Rocca, WA
通讯作者：
Rocca, WA
影响因子：
4.1
作者：
Postuma, R. B.;Montplaisir, J.
通讯作者：
Montplaisir, J.