Jaakkola E, Herzberg I, Laiho K, Barnardo M C N M, Pointon J J, Kauppi M, Kaarela K, Tuomilehto-Wolf E, Tuomilehto J, Wordsworth B P, Brown M A
Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford, United Kingdom.
Ann Rheum Dis. 2006 Jun;65(6):775-80. doi: 10.1136/ard.2005.041103. Epub 2005 Oct 25.
To determine the influence of HLA-B27 homozygosity and HLA-DRB1 alleles in the susceptibility to, and severity of, ankylosing spondylitis in a Finnish population.
673 individuals from 261 families with ankylosing spondylitis were genotyped for HLA-DRB1 alleles and HLA-B27 heterozygosity/homozygosity. The frequencies of HLA-B27 homozygotes in probands from these families were compared with the expected number of HLA-B27 homozygotes in controls under Hardy-Weinberg equilibrium (HWE). The effect of HLA-DRB1 alleles was assessed using a logistic regression procedure conditioned on HLA-B27 and case-control analysis.
HLA-B27 was detected in 93% of cases of ankylosing spondylitis. An overrepresentation of HLA-B27 homozygotes was noted in ankylosing spondylitis (11%) compared with the expected number of HLA-B27 homozygotes under HWE (4%) (odds ratio (OR) = 3.3 (95% confidence interval, 1.6 to 6.8), p = 0.002). HLA-B27 homozygosity was marginally associated with reduced BASDAI (HLA-B27 homozygotes, 4.5 (1.6); HLA-B27 heterozygotes, 5.4 (1.8) (mean (SD)), p = 0.05). Acute anterior uveitis (AAU) was present in significantly more HLA-B27 positive cases (50%) than HLA-B27 negative cases (16%) (OR = 5.4 (1.7 to 17), p<0.004). HLA-B27 positive cases had a lower average age of symptom onset (26.7 (8.0) years) compared with HLA-B27 negative cases (35.7 (11.2) years) (p<0.0001).
HLA-B27 homozygosity is associated with a moderately increased risk of ankylosing spondylitis compared with HLA-B27 heterozygosity. HLA-B27 positive cases had an earlier age of onset of ankylosing spondylitis than HLA-B27 negative cases and were more likely to develop AAU. HLA-DRB1 alleles may influence the age of symptom onset of ankylosing spondylitis.
确定HLA - B27纯合性和HLA - DRB1等位基因对芬兰人群强直性脊柱炎易感性及严重程度的影响。
对来自261个强直性脊柱炎家庭的673名个体进行HLA - DRB1等位基因以及HLA - B27杂合性/纯合性基因分型。将这些家庭中先证者的HLA - B27纯合子频率与处于哈迪 - 温伯格平衡（HWE）状态下对照组中预期的HLA - B27纯合子数量进行比较。使用基于HLA - B27的逻辑回归程序和病例对照分析来评估HLA - DRB1等位基因的作用。
在93%的强直性脊柱炎病例中检测到HLA - B27。与HWE状态下预期的HLA - B27纯合子数量（4%）相比，强直性脊柱炎患者中HLA - B27纯合子出现比例过高（11%）（优势比（OR） = 3.3（95%置信区间，1.6至6.8），p = 0.002）。HLA - B27纯合性与BASDAI降低存在微弱关联（HLA - B27纯合子，4.5（1.6）；HLA - B27杂合子，5.4（1.8）（均值（标准差）），p = 0.05）。HLA - B27阳性病例中急性前葡萄膜炎（AAU）的发生率（50%）显著高于HLA - B27阴性病例（16%）（OR = 5.4（1.7至17），p<0.004）。与HLA - B27阴性病例（35.7（11.2）岁）相比，HLA - B27阳性病例症状开始的平均年龄更低（26.7（8.0）岁）（p<0.0001）。
与HLA - B27杂合性相比，HLA - B27纯合性与强直性脊柱炎风险适度增加相关。HLA - B27阳性病例强直性脊柱炎的发病年龄早于HLA - B27阴性病例，且更易发生AAU。HLA - DRB1等位基因可能影响强直性脊柱炎症状开始的年龄。
