Brown Matthew A, Brophy Sinead, Bradbury Linda, Hamersma Jasmin, Timms Andrew, Laval Steven, Cardon Lon, Calin Andrei, Wordsworth B Paul
Musculoskeletal Sciences, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Headington OX3 7BN, UK.
Arthritis Rheum. 2003 Aug;48(8):2234-9. doi: 10.1002/art.11106.
To identify genomic regions linked with determinants of age at symptom onset, disease activity, and functional impairment in ankylosing spondylitis (AS).
A whole genome linkage scan was performed in 188 affected sibling pair families with 454 affected individuals. Traits assessed were age at symptom onset, disease activity assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and functional impairment assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI). Parametric and nonparametric quantitative linkage analysis was performed using parameters defined in a previous segregation study.
Heritabilities of the traits studied in this data set were as follows: BASDAI 0.49 (P = 0.0001, 95% confidence interval [95% CI] 0.23-0.75), BASFI 0.76 (P = 10(-7), 95% CI 0.49-1.0), and age at symptom onset 0.33 (P = 0.005, 95% CI 0.04-0.62). No linkage was observed between the major histocompatibility complex (MHC) and any of the traits studied (logarithm of odds [LOD] score <1.0). "Significant" linkage (LOD score 4.0) was observed between a region on chromosome 18p and the BASDAI. Age at symptom onset showed "suggestive" linkage to chromosome 11p (LOD score 3.3). Maximum linkage with the BASFI was seen at chromosome 2q (LOD score 2.9).
In contrast to the genetic determinants of susceptibility to AS, clinical manifestations of the disease measured by the BASDAI, BASFI, and age at symptom onset are largely determined by a small number of genes not encoded within the MHC.
确定与强直性脊柱炎（AS）症状出现年龄、疾病活动度及功能损害的决定因素相关的基因组区域。
对188个患病同胞对家庭中的454名患病个体进行了全基因组连锁扫描。评估的性状包括症状出现年龄、通过巴斯强直性脊柱炎疾病活动指数（BASDAI）评估的疾病活动度以及通过巴斯强直性脊柱炎功能指数（BASFI）评估的功能损害。使用先前分离研究中定义的参数进行参数化和非参数化定量连锁分析。
该数据集中所研究性状的遗传力如下：BASDAI为0.49（P = 0.0001，95%置信区间[95%CI]0.23 - 0.75），BASFI为0.76（P = 10⁻⁷，95%CI 0.49 - 1.0），症状出现年龄为0.33（P = 0.005，95%CI 0.04 - 0.62）。未观察到主要组织相容性复合体（MHC）与所研究的任何性状之间存在连锁关系（优势对数[LOD]得分<1.0）。在18号染色体p区域与BASDAI之间观察到“显著”连锁（LOD得分4.0）。症状出现年龄与11号染色体p区域显示“提示性”连锁（LOD得分3.3）。与BASFI的最大连锁出现在2号染色体q区域（LOD得分2.9）。
与AS易感性的遗传决定因素不同，通过BASDAI、BASFI和症状出现年龄衡量的该疾病临床表现很大程度上由少数不在MHC内编码的基因决定。
