LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease.

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_454875FEE9D5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease.
Périodique
Neurogenetics
Auteur(s)
Vilariño-Güell C., Wider C., Ross O.A., Jasinska-Myga B., Kachergus J., Cobb S.A., Soto-Ortolaza A.I., Behrouz B., Heckman M.G., Diehl N.N., Testa C.M., Wszolek Z.K., Uitti R.J., Jankovic J., Louis E.D., Clark L.N., Rajput A., Farrer M.J.
ISSN
1364-6753 ([electronic])
1364-6745 ([linking])
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
11
Numéro
4
Pages
401-408
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Genetic variation in the leucine-rich repeat and Ig domain containing 1 gene (LINGO1) was recently associated with an increased risk of developing essential tremor (ET) and Parkinson disease (PD). Herein, we performed a comprehensive study of LINGO1 and its paralog LINGO2 in ET and PD by sequencing both genes in patients (ET, n=95; PD, n=96) and by examining haplotype-tagging single-nucleotide polymorphisms (tSNPs) in a multicenter North American series of patients (ET, n=1,247; PD, n= 633) and controls (n=642). The sequencing study identified six novel coding variants in LINGO1 (p.S4C, p.V107M, p.A277T, p.R423R, p.G537A, p.D610D) and three in LINGO2 (p.D135D, p.P217P, p.V565V), however segregation analysis did not support pathogenicity. The association study employed 16 tSNPs at the LINGO1 locus and 21 at the LINGO2 locus. One variant in LINGO1 (rs9652490) displayed evidence of an association with ET (odds ratio (OR) =0.63; P=0.026) and PD (OR=0.54; P=0.016). Additionally, four other tSNPs in LINGO1 and one in LINGO2 were associated with ET and one tSNP in LINGO2 associated with PD (P<0.05). Further analysis identified one tSNP in LINGO1 and two in LINGO2 which influenced age at onset of ET and two tSNPs in LINGO1 which altered age at onset of PD (P<0.05). Our results support a role for LINGO1 and LINGO2 in determining risk for and perhaps age at onset of ET and PD. Further studies are warranted to confirm these findings and to determine the pathogenic mechanisms involved.
Pubmed
Web of science
Création de la notice
24/09/2010 18:53
Dernière modification de la notice
03/03/2018 16:45
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