Gain-of-function of P2X7 receptor gene variants in multiple sclerosis

被引：61

作者：

Oyanguren-Desez, Olatz ^{[1
,2
,3
]}

Rodriguez-Antigueedad, Alfredo ^{[4
]}

Villoslada, Pablo ^{[5
]}

Domercq, Maria ^{[1
,2
]}

Alberdi, Elena ^{[1
,2
,3
]}

Matute, Carlos ^{[1
,2
,3
]}

机构：

[1] Univ Basque Country, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Leioa 48940, Spain

[2] Univ Basque Country, Dept Neurociencias, Leioa 48940, Spain

[3] Neurotek, Zamudio, Spain

[4] Hosp Basurto, Serv Neurol, Bilbao, Spain

[5] Hosp Clin Barcelona, Barcelona, Spain

来源：

CELL CALCIUM | 2011年 / 50卷 / 05期

关键词：

P2X7; receptors; Gene polymorphisms; Calcium permeability; Electrophysiology; Dye uptake; Multiple sclerosis; P2X(7) RECEPTOR; EXPRESSION; GLUTAMATE; OLIGODENDROCYTES; INHIBITION;

D O I：

10.1016/j.ceca.2011.08.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We have previously shown that P2X7 receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates chronic experimental autoimmune encephalomyelitis. Here, we have explored the putative association of functionally relevant single nucleotide polymorphisms of the P2X7 receptor gene with multiple sclerosis. We found that T allele of rs17525809 polymorphism, which yields an Ala-76 to Val change in the extracellular domain, is more frequent in multiple sclerosis patients than in controls. Importantly, P2X7 variants with Val show a gain-of-function consisting in higher calcium permeability, larger electrophysiological responses and higher ethidium uptake, and enhance the effect of the also gain-of-function His-155 to Tyr substitution (rs208294) in the haplotype formed by these two variants. These findings may contribute to define the genetic background predisposing for multiple sclerosis and its pathophysiology. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：468 / 472

页数：5