Susceptibility to ankylosing spondylitis in twins - The role of genes, HLA, and the environment
Susceptibility to ankylosing spondylitis in twins - The role of genes, HLA, and the environment
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DOI：
10.1002/art.1780401015
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发表时间：
1997-10-01
影响因子：
--
通讯作者：
Wordsworth, P
中科院分区：
文献类型：
--
作者：
Brown, MA;Kennedy, LG;Wordsworth, P
Objective.确定遗传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确定患有AS的双胞胎，进行临床和放射学检查以确立诊断，并使用经验证的评分系统的组合评估疾病严重程度，通过使用序列特异性引物的聚合酶链反应进行HLA-B27、HLA-B60和HLA-DR 1的HLA分型，并使用微卫星标记评估接合性，遗传和环境的方差分量进行了评估与程序Mx，使用数据从这个和以前的双胞胎与AS的研究。8对同卵（MZ）双胞胎中有6对是疾病一致的，而15对B27阳性双卵（DZ）双胞胎中有4对（27%）和32对DZ双胞胎中有4对（12.5%）是疾病一致的。与疾病一致的DZ双胞胎相比，疾病一致的MZ双胞胎在疾病发作时的年龄和所有疾病严重程度评分的相似性无显著增加，HLA-B27和B60与先证者的疾病相关，而疾病一致率在DZ双胞胎中显著增加，其中双胞胎中的共同双胞胎B27和DR 1均为阳性。加性遗传效应对群体方差的贡献率为97%。AS的易感性主要由基因决定，而引发该疾病的环境因素可能无处不在。HLA-B27占AS总体遗传易感性的一小部分。
Objective. To determine the relative effects of genetic and environmental factors in susceptibility to ankylosing spondylitis (AS).Methods. 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.Results. 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,Conclusion. 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.