Brown M A, Kennedy L G, MacGregor A J, Darke C, Duncan E, Shatford J L, Taylor A, Calin A, Wordsworth P
Wellcome Trust Centre for Human Genetics, Headington, UK.
Arthritis Rheum. 1997 Oct;40(10):1823-8. doi: 10.1002/art.1780401015.
To determine the relative effects of genetic and environmental factors in susceptibility to ankylosing spondylitis (AS).
Twins with AS were identified from the Royal National Hospital for Rheumatic Diseases database. Clinical and radiographic examinations were performed to establish diagnoses, and disease severity was assessed using a combination of validated scoring systems. HLA typing for HLA-B27, HLA-B60, and HLA-DR1 was performed by polymerase chain reaction with sequence-specific primers, and zygosity was assessed using microsatellite markers. Genetic and environmental variance components were assessed with the program Mx, using data from this and previous studies of twins with AS.
Six of 8 monozygotic (MZ) twin pairs were disease concordant, compared with 4 of 15 B27-positive dizygotic (DZ) twin pairs (27%) and 4 of 32 DZ twin pairs overall (12.5%). Nonsignificant increases in similarity with regard to age at disease onset and all of the disease severity scores assessed were noted in disease-concordant MZ twins compared with concordant DZ twins. HLA-B27 and B60 were associated with the disease in probands, and the rate of disease concordance was significantly increased among DZ twin pairs in which the co-twin was positive for both B27 and DR1. Additive genetic effects were estimated to contribute 97% of the population variance.
Susceptibility to AS is largely genetically determined, and the environmental trigger for the disease is probably ubiquitous. HLA-B27 accounts for a minority of the overall genetic susceptibility to AS.
确定遗传因素和环境因素在强直性脊柱炎（AS）易感性中的相对作用。
从皇家国立风湿病医院数据库中识别出患有AS的双胞胎。进行临床和影像学检查以确立诊断，并使用经过验证的评分系统组合评估疾病严重程度。通过序列特异性引物聚合酶链反应对HLA-B27、HLA-B60和HLA-DR1进行HLA分型，并使用微卫星标记评估同卵性。使用程序Mx评估遗传和环境方差成分，使用来自本次及之前对AS双胞胎的研究数据。
8对单卵（MZ）双胞胎中有6对疾病一致，相比之下，15对B27阳性双卵（DZ）双胞胎中有4对（27%），总体32对DZ双胞胎中有4对（12.5%）。与疾病一致的DZ双胞胎相比，疾病一致的MZ双胞胎在疾病发病年龄和所有评估的疾病严重程度评分方面的相似性有非显著增加。HLA-B27和B60与先证者的疾病相关，并且在双胞胎中疾病一致率在其同胞同时为B27和DR1阳性的DZ双胞胎对中显著增加。估计加性遗传效应占总体方差的97%。
AS易感性很大程度上由遗传决定，并且该疾病的环境触发因素可能普遍存在。HLA-B27占AS总体遗传易感性的一小部分。
