Singal D P, Li J, Zhu Y
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Arch Immunol Ther Exp (Warsz). 1999;47(5):307-11.
Rheumatoid arthritis (RA) is a common disabling disorder of unknown etiology. In the past 2 decades, a number of studies have examined the genetic basis for RA. One major focus of these studies has been to identify genes within the MHC class II (HLA-DR) chromosomal region, which confer susceptibility/resistance to RA. A strong association between HLA-DR4 and adult seropositive RA has been observed in majority of populations. In addition, there is evidence of a positive association between HLA-DR1 and RA. On the basis of prevalence of DR1 (B10101) and of subtypes of DR4 (B10401, B10404 and B10405), it has been suggested that a five amino acid sequence motif (QKRAA/QRRAA) from position 70 to 74 in the third hypervariable region of DRbeta1 molecules is associated with susceptibility to RA. These associations between RA and HLA-DR genes are however incomplete in that about 1/4 of patients do not carry RA-susceptibility DRB1 epitope. Since MHC class III region contains genes that are involved in immune response, we have recently examined the role of a number of microsatellites (D6S273, Bat2, TNFa) and HSP70 promoter region alleles in susceptibility to RA. The results demonstrate that two regions in MHC, class II (DRbeta1) and class III (D6S273, HSP70, Bat2, TNFa) more completely define the risk for development of RA.
类风湿性关节炎（RA）是一种病因不明的常见致残性疾病。在过去20年里，许多研究探讨了RA的遗传基础。这些研究的一个主要重点是确定MHC II类（HLA - DR）染色体区域内赋予RA易感性/抗性的基因。在大多数人群中都观察到HLA - DR4与成人血清阳性RA之间存在强烈关联。此外，有证据表明HLA - DR1与RA之间存在正相关。根据DR1（B10101）和DR4亚型（B10401、B10404和B10405）的流行情况，有人提出DRβ1分子第三个高变区第70至74位的一个五氨基酸序列基序（QKRAA/QRRAA）与RA易感性相关。然而，RA与HLA - DR基因之间的这些关联并不完全，因为约四分之一的患者不携带RA易感DRB1表位。由于MHC III类区域包含参与免疫反应的基因，我们最近研究了一些微卫星（D6S273、Bat2、TNFα）和HSP70启动子区域等位基因在RA易感性中的作用。结果表明，MHC中的两个区域，II类（DRβ1）和III类（D6S273、HSP70、Bat2、TNFα）更全面地确定了发生RA的风险。
