Department of Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy and SCBI- Rheumatology Department, Cluj-Napoca, Romania.
PLoS One. 2012;7(9):e43428. doi: 10.1371/journal.pone.0043428. Epub 2012 Sep 12.
Functional severity in ankylosing spondylitis (AS) patients is variable and difficult to predict early. The aim of our study was to assess whether a combination of baseline clinical factors and genetic markers may predict the development of severe functional status in AS. We performed a cross-sectional association study on AS patients included in the Spanish National Registry of Spondyloarthropathies--REGISPONSER. Bath Ankylosing Spondylitis Functional Index (BASFI) was standardized by adjusting for disease duration since the first symptoms (BASFI/t). We considered as severe functional status the values of BASFI/t in the top of the 60th (p60), 65th (p65), 70th (p70), and 75th (p75) percentile. We selected 384 single nucleotide polymorphisms (SNPs) distributed in 190 genes to be analyzed. The study cohort included 456 patients with mean age 50.8(± 10.5) years and with mean disease duration since first symptoms 24.7 (± 10.1) years. Older age at disease onset and neck pain at baseline showed statistical significant association with severe BASFI/t. Polymorphisms associated in the allele frequencies test with severe BASFI/t in all classifications were: rs2542151 (p60 [P = .04], p65 [P = .04], p70 [P = .001] and p75 [P = .001]) and rs2254441 (p60 [P = .004], p65 [P = .02], p70 [P = .01] and p75 [P<.001]).. Genotype association, after adjustment for covariates, found an association in three of the four patients' classifications for rs2542151 and in two of the classifications for rs2254441.Forward logistic regression did not identify any model with a good predictive power for severe functional development.In our study we identified clinical factors and 24 polymorphisms associated with development of severe functional status in AS patients. Validation of these results in other cohorts is required.
强直性脊柱炎（AS）患者的功能严重程度存在差异，且难以早期预测。本研究旨在评估基线临床因素和遗传标志物的组合是否可预测 AS 患者功能严重程度的发展。我们对纳入西班牙脊柱关节病国家注册中心（REGISPONSER）的 AS 患者进行了横断面关联研究。Bath 强直性脊柱炎功能指数（BASFI）通过调整自首发症状以来的疾病持续时间（BASFI/t）进行标准化。我们将 BASFI/t 值处于第 60 百分位（p60）、第 65 百分位（p65）、第 70 百分位（p70）和第 75 百分位（p75）的患者定义为功能严重程度。我们选择了分布于 190 个基因的 384 个单核苷酸多态性（SNP）进行分析。该研究队列纳入了 456 例平均年龄 50.8（±10.5）岁、自首发症状以来平均疾病持续时间为 24.7（±10.1）年的患者。发病年龄较大和基线时颈部疼痛与严重 BASFI/t 有统计学显著相关性。在所有分类中，与严重 BASFI/t 相关的等位基因频率检测中的 SNP 为：rs2542151（p60 [P=.04]，p65 [P=.04]，p70 [P=.001]和 p75 [P=.001]）和 rs2254441（p60 [P=.004]，p65 [P=.02]，p70 [P=.01]和 p75 [P<.001]）。经协变量调整后的基因型相关性分析发现，rs2542151 在四个患者分类中的三个和 rs2254441 在两个分类中与严重功能发展相关。向前逻辑回归未确定任何具有良好预测能力的严重功能发展模型。在本研究中，我们确定了与 AS 患者严重功能状态发展相关的临床因素和 24 个多态性。需要在其他队列中验证这些结果。
