对氧磷酶
肌萎缩侧索硬化
单核苷酸多态性
遗传学
单倍型
电源1
SOD1
生物
基因簇
基因
氧化应激
等位基因
疾病
医学
基因型
内科学
内分泌学
突变体
作者
Paul N. Valdmanis,Edor Kabashi,A. Dyck,Pascale Hince,J. Lee,Patrick A. Dion,Monique L. D'Amour,F Souchon,Julie Bouchard,François Salachas,Vincent Meininger,Peter M. Andersen,William Camu,Nicolas Dupré,Guy A. Rouleau
出处
期刊:Neurology
[Ovid Technologies (Wolters Kluwer)]
日期:2008-08-11
卷期号:71 (7): 514-520
被引量:59
标识
DOI:10.1212/01.wnl.0000324997.21272.0c
摘要
The paraoxonase gene cluster on chromosome 7 comprising the PON1-3 genes is an attractive candidate for association in amyotrophic lateral sclerosis (ALS) given the role of paraoxonase genes during the response to oxidative stress and their contribution to the enzymatic break down of nerve toxins. Oxidative stress is considered one of the mechanisms involved in ALS pathogenesis. Evidence for this includes the fact that mutations of SOD1, which normally reduce the production of toxic superoxide anion, account for 12% to 23% of familial cases in ALS. In addition, PON variants were shown to be associated with susceptibility to ALS in several North American and European populations.We extended this analysis to examine 20 single nucleotide polymorphisms (SNPs) across the PON gene cluster in a set of patients from France (480 cases, 475 controls), Quebec (159 cases, 95 controls), and Sweden (558 cases, 506 controls).Although individual SNPs were not considered associated on their own, a haplotype of SNPs at the C-terminal portion of PON2 that includes the PON2 C311S amino acid change was significant in the French (p value 0.0075) and Quebec (p value 0.026) populations as well as all three populations combined (p value 1.69 x 10(-6)). Stratification of the samples showed that this variation was pertinent to ALS susceptibility as a whole, and not to a particular subset of patients.These findings contribute to the increasing weight of evidence that genetic variants in the paraoxonase gene cluster are associated with amyotrophic lateral sclerosis.
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