Brown M A, Kennedy L G, Darke C, Gibson K, Pile K D, Shatford J L, Taylor A, Calin A, Wordsworth B P
Wellcome Trust Centre for Human Genetics, Headington, UK.
Arthritis Rheum. 1998 Mar;41(3):460-5. doi: 10.1002/1529-0131(199803)41:3<460::AID-ART12>3.0.CO;2-X.
To analyze the effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis (AS).
Three hundred sixty-three white British AS patients were studied; 149 were carefully assessed for a range of clinical manifestations, and disease severity was assessed using a structured questionnaire. Limited HLA class I typing and complete HLA-DR typing were performed using DNA-based methods. HLA data from 13,634 healthy white British bone marrow donors were used for comparison.
A significant association between DR1 and AS was found, independent of HLA-B27 (overall odds ratio [OR] 1.4, 95% confidence interval [95% CI] 1.1-1.8, P = 0.02; relative risk [RR] 2.7, 95% CI 1.5-4.8, P = 6 x 10(-4) among homozygotes; RR 2.1, 95% CI 1.5-2.8, P = 5 x 10(-6) among heterozygotes). A large but weakly significant association between DR8 and AS was noted, particularly among DR8 homozygotes (RR 6.8, 95% CI 1.6-29.2, P = 0.01 among homozygotes; RR 1.6, 95% CI 1.0-2.7, P = 0.07 among heterozygotes). A negative association with DR12 (OR 0.22, 95% CI 0.09-0.5, P = 0.001) was noted. HLA-DR7 was associated with younger age at onset of disease (mean age at onset 18 years for DR7-positive patients and 23 years for DR7-negative patients; Z score 3.21, P = 0.001). No other HLA class I or class II associations with disease severity or with different clinical manifestations of AS were found.
The results of this study suggest that HLA-DR genes may have a weak effect on susceptibility to AS independent of HLA-B27, but do not support suggestions that they affect disease severity or different clinical manifestations.
分析HLA - DR基因对强直性脊柱炎（AS）易感性及严重程度的影响。
对363例英国白人AS患者进行研究；其中149例针对一系列临床表现进行了详细评估，并使用结构化问卷对疾病严重程度进行评估。采用基于DNA的方法进行有限的HLA - I类分型和完整的HLA - DR分型。将来自13634名健康英国白人骨髓供者的HLA数据用于比较。
发现DR1与AS之间存在显著关联，独立于HLA - B27（总体比值比[OR] 1.4，95%置信区间[95%CI] 1.1 - 1.8，P = 0.02；纯合子中的相对风险[RR] 2.7，95%CI 1.5 - 4.8，P = 6×10⁻⁴；杂合子中的RR 2.1，95%CI 1.5 - 2.8，P = 5×10⁻⁶）。注意到DR8与AS之间存在较大但弱显著的关联，特别是在DR8纯合子中（纯合子中的RR 6.8，95%CI 1.6 - 29.2，P = 0.01；杂合子中的RR 1.6，95%CI 1.0 - 2.7，P = 0.07）。注意到与DR12呈负相关（OR 0.22，95%CI 0.09 - 0.5，P = 0.001）。HLA - DR7与疾病发病年龄较小相关（DR7阳性患者的平均发病年龄为18岁，DR7阴性患者为23岁；Z值3.21，P = 0.001）。未发现其他HLA - I类或II类基因与疾病严重程度或AS的不同临床表现相关。
本研究结果表明，HLA - DR基因可能独立于HLA - B27对AS易感性有微弱影响，但不支持其影响疾病严重程度或不同临床表现的观点。
