Mattey D L, Dawes P T, Gonzalez-Gay M A, Garcia-Porrua C, Thomson W, Hajeer A H, Ollier W E
Staffordshire Rheumatology Centre, Stoke-on-Trent, England, UK.
J Rheumatol. 2001 Feb;28(2):232-9.
To determine whether the association between rheumatoid arthritis (RA) and HLA-DRB1 is influenced by the amino acid residue encoded at position 70 (beta70) of the third hypervariable region (HVR3) of the HLA-DRbeta chain.
The frequencies of HLA-DRB1 alleles encoding different amino acid residues at beta70 were compared between patients with RA and controls in a population from the UK and in a confirmatory population from northwestern Spain. HLA-DRB1 typing was done by polymerase chain reaction methods on 476 clinic based patients with RA and 180 healthy controls from Staffordshire and Cheshire in the UK, and on 179 clinic patients and 145 controls from Lugo, Spain. Associations were investigated using chi-square analyses and regression analyses. The extended Mantel-Haenszel procedure was used for trend analysis.
Carriage of 2 shared epitope (SE)+ alleles encoding a glutamine at beta70 (Q70SE+/Q70SE+) was associated with the greatest risk of RA in the UK and Spanish population (odds ratios 7.93 and 4.66, respectively), while possession of 2 SE- alleles encoding an aspartic acid at beta70 (D70SE-D70SE-) was associated with the lowest risk (OR 0.23 and 0.34, respectively). In individuals carrying one SE+ allele and an accompanying D70SE- allele there was no increased risk of developing RA [OR 0.93 (UK) and 1.30 (Spain)]. Possession of D70SE- was more strongly protective than possession of Q70SE. Analysis of trend indicated that the strength of association of different DRB1 genotypes with RA could be ranked in order (from Q70SE+/Q70SE+ to D70SE-/D70SE-) according to which amino acid residues were encoded at beta70, and whether or not they formed part of a SE sequence. The severity of radiographic damage could not be ranked in the same fashion.
The amino acid residue at position 70 of the HVR3 in HLA-DRbeta molecules influences susceptibility to RA. The strength of the association of DRB1 genotypes with RA is dependent not only on SE status, but also on which amino acid residues are encoded at beta70 of the DRB1 alleles. Presence of an aspartic acid residue at beta70 protects against development of RA. However, the severity of erosive damage does not appear to be associated with the amino acid substitution at 1370.
确定类风湿关节炎（RA）与HLA - DRB1之间的关联是否受HLA - DRβ链第三高变区（HVR3）第70位（β70）编码的氨基酸残基影响。
比较来自英国人群和西班牙西北部验证人群中RA患者与对照者之间编码β70不同氨基酸残基的HLA - DRB1等位基因频率。采用聚合酶链反应方法对英国斯塔福德郡和柴郡的476例临床诊断的RA患者及180例健康对照者，以及西班牙卢戈的179例临床患者和145例对照者进行HLA - DRB1分型。使用卡方分析和回归分析研究关联性。采用扩展的Mantel - Haenszel程序进行趋势分析。
在英国和西班牙人群中，携带两个在β70编码谷氨酰胺的共享表位（SE）+等位基因（Q70SE + /Q70SE +）与患RA的风险最高相关（优势比分别为7.93和4.66），而携带两个在β70编码天冬氨酸的SE -等位基因（D70SE - D70SE -）与风险最低相关（OR分别为0.23和0.34）。在携带一个SE +等位基因和一个伴随的D70SE -等位基因的个体中，患RA的风险没有增加[OR 0.93（英国）和1.30（西班牙）]。拥有D70SE -的保护作用比拥有Q70SE更强。趋势分析表明，不同DRB1基因型与RA的关联强度可根据β70编码的氨基酸残基以及它们是否构成SE序列的一部分，按顺序（从Q70SE + /Q70SE +到D70SE - /D70SE -）排列。影像学损伤的严重程度不能以相同方式排列。
HLA - DRβ分子中HVR3第70位的氨基酸残基影响对RA的易感性。DRB1基因型与RA的关联强度不仅取决于SE状态，还取决于DRB1等位基因β70编码的氨基酸残基。β70处存在天冬氨酸残基可预防RA的发生。然而，侵蚀性损伤的严重程度似乎与β70处的氨基酸替代无关。
