Investigating the role of the HLA-Cw*06 and HLA-DRB1 genes in susceptibility to psoriatic arthritis:: comparison with psoriasis and undifferentiated inflammatory arthritis
Investigating the role of the HLA-Cw*06 and HLA-DRB1 genes in susceptibility to psoriatic arthritis:: comparison with psoriasis and undifferentiated inflammatory arthritis
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DOI：
10.1136/ard.2007.071399
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发表时间：
2008-05-01
影响因子：
27.4
通讯作者：
Bruce, I. N.
中科院分区：
文献类型：
--
作者：
Ho, P. Y. P. C.;Barton, A.;Bruce, I. N.
目的：早发型（I型）银屑病发病年龄（40岁）与HLA-Cw*06相关，而共享表位（SE）与类风湿关节炎易感性相关。我们的目的是探讨HLA-Cw*06和HLA-DRB1基因（包括SE）在银屑病关节炎（PsA）易感性中的作用。方法：采用病例-对照关联研究，比较PsA患者（n = 480）、银屑病患者（n = 611）和健康对照组（n = 166）的HLA-Cw*06表型频率。同样，在HLA-DRB1位点，比较PsA （n = 480）、早期未分化炎性关节炎（n = 1621）和健康对照（n = 537）患者的表型和SE频率。结果：HLA-Cw*06表型与I型牛皮癣相关（OR 6.9, 95% CI 4.4, 11.1, p = 2.2 × 10(-21)），与PsA患者患有I型牛皮癣相关（OR 5.0, 95% CI 3.2, 7.9, p = 4.39 × 10(-13)），但与PsA患者患有II型牛皮癣无关（发病年龄为40岁）。HLA-DRB1*07与HLA-Cw*06的连锁不平衡也与PsA合并I型银屑病患者相关（OR 2.7, 95% CI 2.1, 3.7, p < 0.00001）。HLA-DRB1*04等位基因和SE与未分化炎性关节炎相关，与PsA无关。结论：SE不是PsA易感位点。HLA-Cw*06和HLA-DRB1*07与PsA合并I型银屑病患者相关，提示其主要与银屑病发病年龄相关。因此，患有PsA的I型牛皮癣患者与患有II型牛皮癣的患者具有不同的遗传背景，在未来研究PsA遗传易感性的研究中需要对此进行调整。
Objective: Psoriasis of early onset (type I; age of onset (40 years) is associated with HLA-Cw*06 while the shared epitope (SE) is associated with rheumatoid arthritis susceptibility. Our aim was to investigate the role of HLA-Cw*06 and HLA-DRB1 genes (including SE) with psoriatic arthritis (PsA) susceptibility.Methods: In a case-control association study, HLA-Cw*06 phenotype frequencies were compared between patients with PsA (n = 480), psoriasis alone (n = 611) and healthy controls (n = 166). Similarly, at the HLA-DRB1 locus, phenotype and SE frequencies were compared in patients with PsA (n = 480), early undifferentiated inflammatory arthritis alone (n = 1621) and healthy controls (n = 537).Results: The HLA-Cw*06 phenotype was associated with type I psoriasis (OR 6.9, 95% CI 4.4, 11.1, p = 2.2 x 10(-21)) and with patients with PsA having type I psoriasis (OR 5.0, 95% CI 3.2, 7.9, p = 4.39 x 10(-13)), but not with patients with PsA having type II psoriasis (age of onset > 40 years). HLA-DRB1*07, in linkage disequilibrium with HLA-Cw*06, was also associated with patients with PsA having type I psoriasis (OR 2.7, 95% CI 2.1, 3.7, p < 0.00001). HLA-DRB1*04 alleles and the SE were associated with undifferentiated inflammatory arthritis but not with PsA.Conclusions: The SE is not a PsA susceptibility locus. HLA-Cw*06 and HLA-DRB1*07 are associated with patients with PsA having type I psoriasis, suggesting that the primary association is with age of onset of psoriasis. Patients with PsA having type I psoriasis, therefore, have a genetic background different to those with type II psoriasis, and adjustment for this is necessary in future studies that investigate the genetic susceptibility of PsA.