Genetic dissection of a rat model for rheumatoid arthritis: significant gender influences on autosomal modifier loci
Genetic dissection of a rat model for rheumatoid arthritis: significant gender influences on autosomal modifier loci
复制标题
DOI：
10.1093/oxfordjournals.hmg.a018915
复制
发表时间：
2000-09-22
影响因子：
3.5
通讯作者：
Wilder, RL
中科院分区：
文献类型：
--
作者：
Furuya, T;Salstrom, JL;Wilder, RL
风湿性关节炎（RA）是一种常见的慢性自身免疫性炎症性疾病，受包括性别在内的遗传因素影响。许多研究表明，RA的遗传风险是由MHC决定的，特别是具有“共享表位”（SE）的II类等位基因和多个非MHC基因座。其他研究表明，类风湿关节炎和其他自身免疫性疾病，特别是胰岛素依赖型糖尿病（IDDM）和自身免疫性甲状腺疾病（ATD），共享遗传风险因素。大鼠胶原诱导性关节炎（CIA）是一种具有许多类似RA特征的实验模型。自发耐糖尿病生物繁殖大鼠BB（DR）引起人们的兴趣，因为它对实验诱导的CIA、IDDM和ATD易感，并且其MHC II类等位基因具有SE。为了探索CIA的遗传学，包括潜在的性别影响和CIA与其他自身免疫性疾病之间的遗传关系，我们在BB（DR）和CIA耐药BN大鼠的F-2后代中进行了CIA调控基因座的全基因组扫描。我们鉴定了10个数量性状基因座（QTL），其中包括5个新的QTL（分别位于第9、10、18号染色体上的Cia 15、Cia 16 *、Cia 17、Cia 18 * 和Cia 19，以及X染色体上的2个），它们调控着CIA的严重程度。我们还确定了四个QTL，包括两个新的（Ciaa 4 * 和Ciaa 5 *，分别在染色体4和5），调节自身抗体滴度大鼠II型胶原蛋白。这些基因座中的许多似乎是性别的影响，大多数共定位与其他几个自身免疫性状基因座。我们的数据支持这样的观点，即多种自身免疫性疾病可能具有共同的遗传风险因素，并表明这些基因座中的许多基因座受性别影响。
Rheumatoid arthritis (RA) is a common, chronic, autoimmune, inflammatory disease that is influenced by genetic factors including gender. Many studies suggest that the genetic risk for RA is determined by the MHC, in particular class II alleles with a 'shared epitope' (SE), and multiple non-MHC loci. Other studies indicate that RA and other autoimmune diseases, in particular insulin-dependent diabetes mellitus (IDDM) and autoimmune thyroid disease (ATD), share genetic risk factors. Rat collagen-induced arthritis (CIA) is an experimental model with many features that resemble RA. The spontaneous diabetes-resistant bio-breeding rat, BB(DR), is of interest because it is susceptible to experimentally induced CIA, IDDM and ATD, and it has an SE in its MHC class II allele. To explore the genetics of CIA, including potential gender influences and the genetic relationships between CIA and other autoimmune diseases, we conducted a genome-wide scan for CIA regulatory loci in the F-2 progeny of BB(DR) and CIA-resistant BN rats. We identified 10 quantitative trait loci (QTLs), including 5 new ones (Cia15, Cia16*, Cia17, Cia18* and Cia19 on chromosomes 9, 10, 18 and two on the X chromosome, respectively), that regulated CIA severity. We also identified four QTLs, including two new ones (Ciaa4* and Ciaa5* on chromosomes 4 and 5, respectively), that regulated autoantibody titer to rat type II collagen. Many of these loci appeared to be gender influenced, and most co-localized with several other autoimmune trait loci. Our data support the view that multiple autoimmune diseases may share genetic risk factors, and suggest that many of these loci are gender influenced.