Katkam Shiva Krishna, Kumaraswami Konda, Rupasree Yedluri, Thishya Kalluri, Rajasekhar Liza, Kutala Vijay Kumar
Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences (NIMS), Hyderabad, Telangana, India.
Department of Rheumatology, Nizam's Institute of Medical Sciences (NIMS), Hyderabad, Telangana, India.
Hum Immunol. 2016 Feb;77(2):158-64. doi: 10.1016/j.humimm.2015.11.002. Epub 2015 Nov 12.
Cytotoxic T lymphocyte associated-antigen (CTLA4) is a potential negative regulatory molecule of T-cells and associated with several autoimmune diseases. Several reports from different ethnic groups showed that the polymorphisms of the CTLA4 gene have been associated with autoimmune diseases including SLE. Therefore, we aimed to investigate the +49 A/G polymorphism in South Indian SLE patients and its association with disease aetiology and serological markers. A total of 534 samples were genotyped for the +49 A/G polymorphism in exon 1 of the CTLA-4 gene through PCR-RFLP method. We found significant association of genotype and allele frequencies with +49 A/G polymorphism in SLE patients. The frequency of the +49 A/G polymorphism rs231775 'GG' genotype was significantly higher in patients with SLE (12.32%) than those in healthy control subjects (4.6%) (OR: 1.797; 95% CI 1.264-2.554; p=0.001). The frequency of mutant allele 'G' also found to be significantly higher in cases (36.01%) than controls (24.92%) (OR: 1.695, 95% CI: 1.298-2.214, p<0.001). We observed significant increase in serum TNF-α, interferon-α, IL-10 and IL-12 in SLE cases compared to controls. We also found a significant association of serum TNF-α, interferon-α, IL-10 and IL-12 with SLE phenotypes. In addition there was a significant increase in serum TNF-α level in "GG" genotype SLE subjects suggesting that it might play a major role in the advancement of SLE disease.
细胞毒性T淋巴细胞相关抗原（CTLA4）是T细胞潜在的负调节分子，与多种自身免疫性疾病相关。来自不同种族群体的几份报告表明，CTLA4基因的多态性与包括系统性红斑狼疮（SLE）在内的自身免疫性疾病有关。因此，我们旨在研究南印度SLE患者中+49 A/G多态性及其与疾病病因和血清学标志物的关联。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对534份样本进行CTLA-4基因外显子1中+49 A/G多态性的基因分型。我们发现SLE患者的基因型和等位基因频率与+49 A/G多态性存在显著关联。SLE患者中+49 A/G多态性rs231775 'GG'基因型的频率（12.32%）显著高于健康对照者（4.6%）（比值比：1.797；95%置信区间1.264 - 2.554；p = 0.001）。突变等位基因“G”的频率在病例组（36.01%）中也显著高于对照组（24.92%）（比值比：1.695，95%置信区间：1.298 - 2.214，p < 0.001）。与对照组相比，我们观察到SLE病例血清肿瘤坏死因子-α（TNF-α）、干扰素-α、白细胞介素-10（IL-10）和白细胞介素-12显著升高。我们还发现血清TNF-α、干扰素-α、IL-10和IL-12与SLE表型存在显著关联。此外，“GG”基因型SLE患者的血清TNF-α水平显著升高，表明它可能在SLE疾病进展中起主要作用。
