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Cdx-2和维生素D受体基因Taq I多态性对肺结核趋化因子表达的调控作用

Regulatory role of Cdx-2 and Taq I polymorphism of vitamin D receptor gene on chemokine expression in pulmonary tuberculosis.

作者信息

Harishankar M, Selvaraj P

机构信息

Department of Immunology, National Institute for Research in Tuberculosis (Formerly Tuberculosis Research Centre), Indian Council of Medical Research, 1, Mayor Sathyamoorthy Road, Chennai 600 031, India.

Department of Immunology, National Institute for Research in Tuberculosis (Formerly Tuberculosis Research Centre), Indian Council of Medical Research, 1, Mayor Sathyamoorthy Road, Chennai 600 031, India.

出版信息

Hum Immunol. 2016 Jun;77(6):498-505. doi: 10.1016/j.humimm.2016.04.008. Epub 2016 Apr 8.

Abstract

Vitamin D receptor (VDR) gene variants have been shown to be regulating the immune response in tuberculosis. We studied the regulatory role of VDR promoter Cdx-2 and 3'UTR TaqI gene variants on chemokine levels from culture filtrate antigen (CFA) stimulated with or without 1,25(OH)2D3 treated peripheral blood mononuclear cells of 50 pulmonary tuberculosis patients (PTB) and 51 normal healthy controls (HCs). In CFA with 1,25(OH)2D3 treated cultures, the MIP-1α, MIP-1β, RANTES levels were significantly decreased in Cdx-2 AA genotype compared to GG genotype, while a significantly increased MIG level was observed in Cdx-2 AA genotype (p<0.05). In TaqI polymorphism, tt genotype significantly decreased MIP-1β and RANTES levels compared to TT genotype. Moreover, a significantly increased level of IP-10 and MIG was observed in TaqI tt genotype compared with TT genotype (p<0.05). The results suggests that the 1,25(OH)2D3 may alter the chemokine response through the VDR polymorphic variants during infection.

摘要

维生素D受体(VDR)基因变异已被证明在结核病中调节免疫反应。我们研究了VDR启动子Cdx - 2和3'UTR TaqI基因变异对50例肺结核患者(PTB)和51例正常健康对照者(HCs)经1,25(OH)2D3处理或未处理的外周血单个核细胞受培养滤液抗原(CFA)刺激后趋化因子水平的调节作用。在经1,25(OH)2D3处理的CFA培养物中,与GG基因型相比,Cdx - 2 AA基因型的MIP - 1α、MIP - 1β、RANTES水平显著降低,而在Cdx - 2 AA基因型中观察到MIG水平显著升高(p<0.05)。在TaqI多态性中,与TT基因型相比,tt基因型显著降低了MIP - 1β和RANTES水平。此外,与TT基因型相比,TaqI tt基因型中IP - 10和MIG水平显著升高(p<0.05)。结果表明,1,25(OH)2D3可能在感染期间通过VDR多态性变异改变趋化因子反应。

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