کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2166175 1091824 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Gain-of-function of P2X7 receptor gene variants in multiple sclerosis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Gain-of-function of P2X7 receptor gene variants in multiple sclerosis
چکیده انگلیسی

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.


► Functionally relevant P2X7 receptor variants are more frequent in multiple sclerosis.
► Multiple sclerosis-associated P2X7 variants show a gain of function.
► P2X7 variants may contribute to the genetic background of multiple sclerosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cell Calcium - Volume 50, Issue 5, November 2011, Pages 468–472
نویسندگان
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