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肿瘤坏死因子-α(-308(GG))、白细胞介素-10(-819(TT))、白细胞介素-10(-1082(GG))和白细胞介素-1受体1(+1970(CC))基因型与北印度人群麻风病易感性及病情进展的关联

Association of TNF-α-(308(GG)), IL-10(-819(TT)), IL-10(-1082(GG)) and IL-1R1(+1970(CC)) genotypes with the susceptibility and progression of leprosy in North Indian population.

作者信息

Tarique Mohd, Naqvi Raza Ali, Santosh K V, Kamal Vineet Kumar, Khanna Neena, Rao D N

机构信息

Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi 110029, India.

Department of Biostatistics, All India Institute of Medical Sciences, AIIMS, New Delhi 110029, India.

出版信息

Cytokine. 2015 May;73(1):61-5. doi: 10.1016/j.cyto.2015.01.014. Epub 2015 Feb 16.

Abstract

Leprosy is an infectious disease caused by M. leprae. We analyzed 48 cytokine polymorphisms in 13 (pro as well as anti-inflammatory) cytokine genes using PCR-SSP assay in 102 leprosy patients and 120 healthy controls with intent to find out a link between cytokine polymorphisms and disease susceptibility. TNF-α (-308) GG, IL-10 (-819) TT, IL-10 (-1082) GG and IL1R (+1970) CC genotypes are found to be predominant (p=0.01, p=0.02, p=0.0001 and p=0.001, respectively) in both tuberculoid as well as lepromatous leprosy patients. This observation suggests these genotypes as play the central role(s) in the progression of disease. CBA assay demonstrates the varied serum concentration of these cytokines with respect to their genotypes. The above genotypes appeared as high producer genotypes in our study. Even in presence of high produce genotypes, TNF-α level are found to be affected/masked by the presence of IL-10 in leprosy patients. Expressional masking of TNF-α is associated with the expression of IL-10 in these patients. This is one the negative impact of SNP-SNP interaction in leprosy patients. Therefore, we can conclude that cytokine gene polymorphisms determine the predisposition to the leprosy progression.

摘要

麻风病是由麻风分枝杆菌引起的一种传染病。我们使用聚合酶链反应-序列特异性引物(PCR-SSP)分析法,对102例麻风病患者和120名健康对照者的13种(促炎和抗炎)细胞因子基因中的48种细胞因子多态性进行了分析,旨在找出细胞因子多态性与疾病易感性之间的联系。在结核样型和瘤型麻风病患者中,均发现肿瘤坏死因子-α(TNF-α)(-308)GG、白细胞介素-10(IL-10)(-819)TT、IL-10(-1082)GG和白细胞介素1受体(IL1R)(+1970)CC基因型占主导地位(分别为p = 0.01、p = 0.02、p = 0.0001和p = 0.001)。这一观察结果表明这些基因型在疾病进展中起核心作用。细胞因子生物活性分析(CBA)显示,这些细胞因子的血清浓度因基因型而异。在我们的研究中,上述基因型表现为高产生基因型。即使存在高产生基因型,在麻风病患者中,TNF-α水平也被发现受到IL-10的影响/掩盖。TNF-α的表达掩盖与这些患者中IL-10的表达相关。这是麻风病患者中单核苷酸多态性-单核苷酸多态性(SNP-SNP)相互作用的负面影响之一。因此,我们可以得出结论,细胞因子基因多态性决定了麻风病进展的易感性。

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