Rheumatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Department of Rheumatology in Östergötland, County Council of Östergötland , Linköping , Sweden.
Scand J Rheumatol. 2013;42(6):465-8. doi: 10.3109/03009742.2013.779020. Epub 2013 Apr 2.
The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is important for interleukin-1beta (IL-1β) processing as part of an innate immune response. Caspase recruitment domain family, member 8 (CARD8) is an inhibitor of nuclear factor kappa B (NF-κB) and possibly also a part of the NLRP3 inflammasome. The objective of this study was to evaluate one single nucleotide polymorphism (SNP) in CARD8 and three SNPs in NLRP3 in ankylosing spondylitis (AS) susceptibility and disease phenotype.
We recruited 492 AS patients from Southern Sweden fulfilling the modified New York criteria for AS, and assessed phenotypic characteristics from medical records and questionnaires. Patients with psoriasis or clinically overt inflammatory bowel disease (IBD) were excluded, as were patients without human leucocyte antigen B27 (HLA-B27). Three NLRP3 SNPs (rs35829419, rs4353135, and rs10733113) and one SNP in CARD8 (rs2043211) were genotyped by commercially available TaqMan assays, and the results compared at genotype and allele levels to those of 793 population-based controls. In a subgroup of the patients (n = 169), faecal calprotectin was assessed as a marker of subclinical intestinal inflammation.
The minor allele (A) of CARD8-C10X (rs2043211) was associated with a decreased risk of AS in a dominant model [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.54-0.94, p = 0.012] and at the allelic level (OR 0.81, 95% CI 0.68-0.97, p = 0.02), but was not associated with levels of faecal calprotectin. There was no association regarding NLRP3 SNPs and AS susceptibility, and none of the investigated SNPs were associated with iritis, anti-tumour necrosis factor (anti-TNF) therapy, or peripheral joint involvement.
In a Swedish population, the minor allele of CARD8-C10X is associated with a decreased risk of AS, but not with levels of faecal calprotectin or disease phenotype.
NOD 样受体家族，富含吡咯烷域的 3（NLRP3）炎性小体对于白细胞介素-1β（IL-1β）的加工很重要，是先天免疫反应的一部分。Caspase 募集域家族，成员 8（CARD8）是核因子 kappa B（NF-κB）的抑制剂，也可能是 NLRP3 炎性小体的一部分。本研究的目的是评估 ankylosing spondylitis（AS）易感性和疾病表型中 CARD8 中的一个单核苷酸多态性（SNP）和 NLRP3 中的三个 SNP。
我们从瑞典南部招募了 492 名符合改良纽约 AS 标准的 AS 患者，并从病历和问卷调查中评估了表型特征。排除了银屑病或临床上明显的炎症性肠病（IBD）患者，以及没有人类白细胞抗原 B27（HLA-B27）的患者。通过商业可用的 TaqMan 检测对三个 NLRP3 SNP（rs35829419、rs4353135 和 rs10733113）和 CARD8 中的一个 SNP（rs2043211）进行了基因分型，并将基因型和等位基因水平的结果与 793 名基于人群的对照进行了比较。在患者的亚组（n = 169）中，评估粪便钙卫蛋白作为亚临床肠道炎症的标志物。
CARD8-C10X（rs2043211）的次要等位基因（A）在显性模型中与 AS 的风险降低相关[比值比（OR）0.74，95%置信区间（CI）0.54-0.94，p = 0.012]和等位基因水平（OR 0.81，95% CI 0.68-0.97，p = 0.02），但与粪便钙卫蛋白水平无关。关于 NLRP3 SNP 和 AS 易感性没有关联，并且没有一个研究的 SNP 与虹膜炎、抗肿瘤坏死因子（anti-TNF）治疗或外周关节受累有关。
在瑞典人群中，CARD8-C10X 的次要等位基因与 AS 的风险降低有关，但与粪便钙卫蛋白水平或疾病表型无关。
