Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India.
Genetic Services Unit, Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India.
Indian J Med Res. 2018 Jun;147(6):560-566. doi: 10.4103/ijmr.IJMR_2025_16.
BACKGROUND & OBJECTIVES: Genetic aberrations disrupting toll-like receptor and interferon homeostasis enhance the risk of systemic lupus erythematosus (SLE). Raised serum interferon-alpha (IFN-α) levels in SLE patients have been ascribed to polymorphism (rs2004640 G/T) in interferon regulatory factor 5 (IRF5) gene, resulting in enhanced transcript splicing. A positive association between IRF5 polymorphism and SLE risk has been reported in many populations. This study was aimed to find out frequency of IRF5 rs2004640 G/T polymorphism in patients with SLE and healthy controls and to assess its influence on susceptibility, clinical and serological characteristics of SLE.
IRF5 rs2004640 (G/T) polymorphism was analyzed in 300 SLE patients and 460 age and sex matched controls by real-time PCR.
The IRF5 rs2004640 (G/T) polymorphism did not confer risk of SLE or influence clinical or serological phenotype. However, the mutant allele conferred a borderline risk to develop thrombocytopenia (odds ratio: 2.05, 95% confidence interval: 0.97-4.3, P=0.06) in patients with SLE.
INTERPRETATION & CONCLUSIONS: Our study revealed that the IRF5 rs2004640 polymorphism was not a risk factor for SLE in population from south India. It may, however, be a useful genetic marker for thrombocytopenia in SLE patients. Although we could not demonstrate susceptibility toward lupus in the presence of IRF5 rs2004640 (G/T) polymorphism, further exploration of the genetic variability of IRF5 may help uncover its pathogenic role in Indian SLE patients.
破坏 Toll 样受体和干扰素稳态的遗传异常会增加系统性红斑狼疮（SLE）的风险。SLE 患者血清中干扰素-α（IFN-α）水平升高归因于干扰素调节因子 5（IRF5）基因的多态性（rs2004640 G/T），导致转录剪接增强。IRF5 多态性与 SLE 风险之间的正相关已在许多人群中得到报道。本研究旨在探讨 IRF5 rs2004640（G/T）多态性在 SLE 患者和健康对照中的频率，并评估其对 SLE 易感性、临床和血清学特征的影响。
通过实时 PCR 分析 300 例 SLE 患者和 460 名年龄和性别匹配的对照中 IRF5 rs2004640（G/T）多态性。
IRF5 rs2004640（G/T）多态性不能赋予 SLE 发病风险或影响临床或血清学表型。然而，突变等位基因赋予 SLE 患者发生血小板减少症的边缘风险（比值比：2.05，95%置信区间：0.97-4.3，P=0.06）。
我们的研究表明，IRF5 rs2004640 多态性不是印度南部人群中 SLE 的危险因素。然而，它可能是 SLE 患者血小板减少症的有用遗传标志物。尽管我们不能证明 IRF5 rs2004640（G/T）多态性存在时对狼疮的易感性，但对 IRF5 遗传变异性的进一步探索可能有助于揭示其在印度 SLE 患者中的致病作用。
