Department of Rheumatology, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Nantong, China.
Clinical Medicine Research Center, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Nantong, China.
Front Immunol. 2022 Apr 5;13:852326. doi: 10.3389/fimmu.2022.852326. eCollection 2022.
Human leucocyte antigen B27 (HLA-B27) is an important biomarker for ankylosing spondylitis (AS). However, delay in the diagnosis of AS is still common in clinical practice. Several single nucleotide polymorphisms (SNPs) in the coding gene of tumor necrosis factor alpha (TNFα) have been reported to be AS susceptibility loci. Our aim was to explore whether SNPs in could be used to improve the performance of HLA-B27 for predicting AS.
Five SNPs (rs1799964, rs1800630, rs1799724, rs1800629, and rs361525) spanning were genotyped by qPCR-Invader assay in 93 AS patients and 107 healthy controls for association analysis and linkage disequilibrium (LD) analysis. Random forest algorithm was utilized to construct the predictive classifiers for AS. was genotyped by PCR-sequence-based typing in a subset of the HLA-B27-positive subjects (38 AS patients and 5 healthy controls).
The T allele of rs1799724 was verified to significantly increase the risk of AS (OR = 4.583, < 0.0001), while the A allele of rs361525 showed an association with the reduced AS risk (OR = 0.168, = 0.009). In addition, the rs1799964-rs1800630-rs1799724-rs1800629-rs361525 haplotype was significantly associated with a higher risk of AS ( < 0.0001). The optimal set of variables for classifiers to predict AS only consisted of HLA-B27. Strong associations with HLA-B27 status were found in both rs1799724 ( < 0.0001) and rs361525 ( = 0.001), and all the analyzed HLA-B27-positive subjects carried or .
In the Chinese Han population, the minor allele T of rs1799724 could increase the risk of AS, while the minor allele A of rs361525 protects individuals from AS. However, the contributions of rs1799724 and rs361525 to AS risk were dependent on HLA-B27 status, suggesting the importance of taking the independence and specificity into consideration in AS susceptibility loci studies.
人类白细胞抗原 B27（HLA-B27）是强直性脊柱炎（AS）的重要生物标志物。然而，AS 的临床诊断延迟仍然很常见。肿瘤坏死因子α（TNFα）编码基因中的几个单核苷酸多态性（SNP）已被报道为 AS 易感基因座。我们的目的是探讨 是否可以使用 中的 SNP 来提高 HLA-B27 预测 AS 的性能。
采用 qPCR-Invader 检测方法对 93 例 AS 患者和 107 例健康对照者的 5 个 SNP（rs1799964、rs1800630、rs1799724、rs1800629 和 rs361525）进行基因分型，进行关联分析和连锁不平衡（LD）分析。随机森林算法用于构建 AS 的预测分类器。在 HLA-B27 阳性患者（38 例 AS 患者和 5 例健康对照者）中，采用 PCR-测序为基础的方法对 进行基因分型。
rs1799724 的 T 等位基因被证实显著增加 AS 的风险（OR=4.583，<0.0001），而 rs361525 的 A 等位基因与降低 AS 的风险相关（OR=0.168，=0.009）。此外，rs1799964-rs1800630-rs1799724-rs1800629-rs361525 单倍型与 AS 风险显著相关（<0.0001）。用于预测 AS 的分类器的最佳变量集仅由 HLA-B27 组成。rs1799724（<0.0001）和 rs361525（=0.001）均与 HLA-B27 状态呈强关联，且所有分析的 HLA-B27 阳性患者均携带 或 。
在中国汉族人群中，rs1799724 的 T 等位基因可能增加 AS 的风险，而 rs361525 的 A 等位基因可保护个体免受 AS 的影响。然而，rs1799724 和 rs361525 对 AS 风险的贡献取决于 HLA-B27 状态，这表明在 AS 易感基因座研究中，考虑独立性和特异性非常重要。
