Variation in the IL7RA and IL2RA genes in German multiple sclerosis patients
Variation in the IL7RA and IL2RA genes in German multiple sclerosis patients
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DOI：
10.1016/j.jaut.2009.01.002
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发表时间：
2009-03-01
影响因子：
12.8
通讯作者：
Epplen, J. T.
中科院分区：
文献类型：
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作者：
Akkad, D. A.;Hoffjan, S.;Epplen, J. T.
白介素7(IL)7和白介素2受体α链(IL7RA，IL2RA)编码基因的变异与多发性硬化(MS)有关。我们评估了这两个基因在一个大型德国多发性硬化症病例对照队列中的作用。用限制性内切酶或TaqMan分析方法对1319例MS患者和908例对照组的IL7RA和IL2RA的5个单核苷酸多态(SNPs)和4个单核苷酸多态(SNPs)进行基因分型，并评估其与MS的相关性。24名受试者进行了实时定量聚合酶链式反应。我们复制了IL7RA外显子6的变异(Rs6897932)与MS的关联，但这种关联仅在原发进展性(Pp)或继发性进展性(Sp)病程的患者中发现(p=0.0004)。表达分析没有显示IL7RA的表达依赖于该基因座的基因类型的差异，而在pp和spMS患者中观察到可溶性受体的表达降低，而与基因无关。在IL2RA基因中，内含子3和7上的SNPs与MS亚型显著相关。综上所述，这些结果证实了LL7RA和LL2RA基因的多态参与了MS的发病机制，并提示IL7RA的变异可能主要影响慢性疾病的病程。(C)2009爱思唯尔有限公司。保留所有权利。
Variation in the genes encoding the interleukin (IL) 7 and IL2 receptor alpha chains (IL7RA, IL2RA) was recently found associated with multiple sclerosis (MS). We evaluated the role of these two genes in a large German MS case-control cohort. Five single nucleotide polymorphisms (SNPs) in IL7RA and four in IL2RA were genotyped in 1319 MS patients and 908 controls by means of restriction enzyme digestion or TaqMan assays and subsequently evaluated for association with MS. IL7RA expression was measured A. a quantitative real time PCR in 24 subjects.We replicated the association of exon 6 variation (rs6897932) in IL7RA with MS. Yet, this association was only found in patients with primary progressive (pp) or secondary progressive (sp) disease course (p = 0.0004). Expression analysis did not show differences in IL7RA expression depending on genotypes at this locus, while reduced expression of the soluble receptor was observed in patients with pp and sp MS irrespective of genotype. In the IL2RA gene, significant associations of SNPs in introns 3 and 7 with MS subtypes were obvious. Together these results confirm involvement of polymorphisms in the lL7RA and lL2RA genes in MS pathogenesis and suggest that IL7RA variation may primarily affect chronic disease courses. (C) 2009 Elsevier Ltd. All rights reserved.