Nossent Johannes C, Sagen-Johnsen Sylvia, Bakland Gunnstein
Department of Rheumatology, University of Western Australia, Sir Charles Gairdner Hospital, Perth, Australia.
Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
Eur J Rheumatol. 2018 Dec 18;6(2):67-70. doi: 10.5152/eurjrheum.2018.18150. Print 2019 Apr.
Variations in the IL-1 alpha (IL-A) gene increase the risk for ankylosing spondylitis (AS), but the pathway underlying this association is not fully understood. As IL-1A is primarily a regulatory cytokine, we investigated the influence of IL-1A gene variation on disease severity and cytokine expression in AS.
This was a cross sectional study of tumor necrosis factor inhibitors (TNFi)-naïve AS patients (n=334, 90% B27 +, age 45 years) fulfilling the modified New York criteria. We recorded demographics, clinical findings, spinal mobility, Bath AS Functional Index (BASFI), and routine lab findings. IL-1A genotyping for three AS-associated single nucleotide polymorphism (SNP; rs2856836, rs17561 and rs1894399) was performed using Taqman RT-PCR, with TNF, IL-6, IL-17A, and IL-23 levels measured using ELISA. Genotypic associations included logistic regression analysis for genotype (codominant model) and global haplotype (threshold 5%) associations with cytokine levels and clinical features.
The three variants were in near complete linkage disequilibrium and formed two only common haplotypes (ACC 67%, GAT 33%). The levels for TNF, IL-6, IL-17A, IL-23, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were similar across genotypes and haplotypes (all p-values >0.4) as were the measures for spinal mobility and BASFI. The TAQ haplotype showed a borderline significant trend with reduced heart disease and mortality during follow-up.
IL-1A gene cluster variations do not have an impact on the clinical disease measures or cytokine levels in AS, suggesting that IL-1A has no direct role in AS.
白细胞介素-1α（IL-A）基因变异会增加强直性脊柱炎（AS）的发病风险，但这种关联背后的机制尚未完全明确。由于IL-1A主要是一种调节性细胞因子，我们研究了IL-1A基因变异对AS疾病严重程度和细胞因子表达的影响。
这是一项横断面研究，研究对象为未使用过肿瘤坏死因子抑制剂（TNFi）的AS患者（n = 334，90%为B27阳性，年龄45岁），符合改良纽约标准。我们记录了人口统计学信息、临床检查结果、脊柱活动度、巴斯强直性脊柱炎功能指数（BASFI）以及常规实验室检查结果。使用Taqman RT-PCR对三个与AS相关的单核苷酸多态性（SNP；rs2856836、rs17561和rs1894399）进行IL-1A基因分型，使用酶联免疫吸附测定法（ELISA）测量肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、白细胞介素-17A（IL-17A）和白细胞介素-23（IL-23）水平。基因分型关联包括对基因型（共显性模型）和全局单倍型（阈值5%）与细胞因子水平及临床特征的逻辑回归分析。
这三个变异几乎完全连锁不平衡，形成了仅有的两种常见单倍型（ACC 67%，GAT 33%）。不同基因型和单倍型的TNF、IL-6、IL-17A、IL-23、C反应蛋白（CRP）和红细胞沉降率（ESR）水平相似（所有p值>0.4），脊柱活动度和BASFI的测量结果也相似。TAQ单倍型在随访期间显示出与心脏病减少和死亡率降低的临界显著趋势。
IL-1A基因簇变异对AS的临床疾病指标或细胞因子水平没有影响，这表明IL-1A在AS中没有直接作用。
