Sequence variation in the transforming growth factor-β1 (TGFB1) gene and multiple sclerosis susceptibility
Sequence variation in the transforming growth factor-β1 (TGFB1) gene and multiple sclerosis susceptibility
复制标题
DOI：
10.1016/s0165-5728(01)00283-1
复制
发表时间：
2001-05-01
影响因子：
3.3
通讯作者：
Oksenberg, JR
中科院分区：
文献类型：
--
作者：
Green, AJ;Barcellos, LF;Oksenberg, JR
多发性硬化症（MS）的基因组筛查已经确定了多个易感区域，支持这种疾病的多基因模型。在ch.19q13处始终观察到连锁的证据，表明该区域存在MS基因。在该区域内编码几个有趣的候选基因，包括转化生长因子β 1（TGFB 1）和白细胞介素-11（ILI 1）。两者都是多功能细胞因子，具有显著且充分表征的免疫调节特性。我们进行了全面的评价内的TGFB 1和IL 11位点和三个紧密侧翼微卫星标记（D19 S421，CEA，D19 S908）在161个严格确定和临床特征的MS多重家庭的连锁（lod评分，同胞对分析）和关联（系谱不平衡检验或PDT）的测试。患者和家庭分层的HLA-DR 2，状态搜索两个位点的相互作用。在DR 2中观察到与CEA的连锁和关联的暗示性证据（分别为lad评分= 1.25，theta = 0.20，p = 0.015），位于距离TGFB 1 0.4chi处。只有积极的家庭。不同的临床表型也进行了检查，TGFB 1单倍型和轻度病程之间存在关联（p = 0.008），提高了TGFB 1或附近基因座可能影响疾病表达的可能性。(C)2001 Elsevier Science B. V.保留所有权利。
Genome screenings in multiple sclerosis (MS) have identified multiple susceptibility regions supporting a polygenic model for this disease. Evidence far Linkage was consistently observed at ch.19q13 suggesting the presence of an MS gene(s) in this region. Several interesting candidate genes are encoded within this region, including transforming growth factor-beta 1 (TGFB1) and interleukin-11 (ILI1). Both are multifunctional cytokines with significant and well-characterized immunomodulatory properties. We performed a comprehensive evaluation of common polymorphisms within the TGFB1 and IL11 loci and three closely flanking microsatellite markers (D19S421, CEA, D19S908) in 161 stringently ascertained and clinically characterized MS multiplex families using tests of both linkage (lod score, sib-pair analysis) and association (pedigree disequilibrium test or PDT). Patients and families were stratified by HLA-DR2, status to search for two-locus interactions. Suggestive evidence for linkage and association to CEA (lad score = 1.25, theta = 0.20, p = 0.015, respectively), located 0.4 chi from TGFB1, was observed in DR2. positive families only. Distinct clinical phenotypes were also examined and an association between a TGFB1 haplotype and a mild disease course was present(p = 0.008), raising the possibility that TGFB1 or a nearby locus may influence disease expression. (C) 2001 Elsevier Science B.V. All rights reserved.