台灣紅斑性狼瘡病患之NLRP3基因多型性

NLRP3 gene polymorphisms and systemic lupus erythematosus in Taiwan

目的：系統性紅斑狼瘡（SLE）是一種複雜的自體免疫疾病，已知其受各種基因中的單核苷酸多態性（SNP）的影響。先前的研究發現，SLE與NOD-、LRR-和pyrin結構域蛋白3（NLRP3）基因中的SNP存在關聯，而該基因在抗微生物發炎反應中起著重要作用。本研究旨在探討三種此類SNP與SLE之間的關係。
方法：我們自單一醫學中心招募了138名SLE患者和165名健康對照者。我們研究了SLE患者的各種臨床和血清學表現以及其三個SNP rs72553859、rs12079994和rs12137901之間的關係。此些SNP通過TaqMan檢測方法進行檢測。
結果：我們發現，對於rs72553859而言，C等位基因對SLE的發病具有保護作用（OR=0.020，p=2.577×10^-13），且此現象獨立於病患是否帶HLA-DR2，這是臺灣患者中已知的SLE風險因子。我們未發現這三個SNP與SLE診斷年齡之間有任何關聯。rs12079994的A等位基因有降低圓盤狀紅斑狼瘡風險方面的趨勢（OR=0.184，p=0.051）。最後，我們研究了這三個SNP與各種自體免疫相關物質濃度之間的關係。我們發現，rs12137901的C等位基因與類風溼因子形成的較高風險相關（OR=5.815，p=0.003）。
結論：NLRP3基因中rs72553859的C等位基因是SLE的保護因子，而rs12137901的C等位基因則與類風溼因子形成的風險增加相關。

Objectives: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is known to be affected by single-nucleotide polymorphisms (SNPs) within various genes. Previous studies have uncovered a relationship between SLE and SNPs within the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) gene, which plays an important role in the antimicrobial inflammatory response. We aimed to examine the associations between three such SNPs and SLE.
Methods: We enrolled 138 patients with SLE and 165 healthy controls from a single medical center. We investigated the relationship between various clinical and serological presentations of SLE and the SNPs rs72553859, rs12079994, and rs12137901. NLRP3 gene polymorphisms were detected using TaqMan assays.
Results: We found that, for the SNP rs72553859, the C allele conferred a protective effect (OR=0.020, p=2.577×10-13) against the development of SLE independent of HLA-DR2, which is a known risk factor for SLE in Taiwanese patients. For all three SNPs we tested, we did not find any association between SNP and age at diagnosis of SLE. The SNP rs12079994 G>A trended towards association with a lower risk for discoid lupus (OR=0.184, p=0.051). Finally, we examined the relationship between the three SNPs and the serological statuses of various autoimmune markers. We found that the C allele of the SNP rs12137901 was associated with a higher risk of formation of rheumatoid factor (OR=5.815, p=0.003).
Conclusions: The C allele of the SNP rs72553859 in the NLRP3 gene is a protective factor for SLE, while the C allele of the SNP rs12137901 is associated with increased risk of rheumatoid factor formation.