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印度北部人群中白细胞介素-10基因启动子多态性与HIV-1感染的遗传关联

Genetic association of IL-10 gene promoter polymorphism and HIV-1 infection in North Indians.

作者信息

Chatterjee Animesh, Rathore Anurag, Sivarama P, Yamamoto Naohiko, Dhole Tapan N

机构信息

Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebarelli Road, Lucknow, 226014, India.

出版信息

J Clin Immunol. 2009 Jan;29(1):71-7. doi: 10.1007/s10875-008-9220-5. Epub 2008 Aug 6.

Abstract

INTRODUCTION

Cytokines play a significant role in host immune defense. IL-10 is an anti-inflammatory, immunomodulatory cytokine that can both stimulate and suppress the immune response and inhibits HIV-1 replication in vivo. Interindividual variations in IL-10 production were genetically contributed to polymorphisms within IL-10 promoter region.

AIMS

The aim of this study was to investigate the association of IL-10 gene promoter -1082 G/A, -819 C/T, and 592 C/A polymorphism on HIV-1 transmission /progression in North Indian individuals.

PATIENTS AND METHODS

A total of 180 HIV-1 seropositive (HSP) stratified on the basis of disease severity (stage I, II, and III), 50 HIV-1 exposed seronegative (HES) and 305 HIV-1 seronegative (HSN) individuals were genotyped for IL-10 gene promoter by polymerase chain reaction-restriction fragment length polymorphism. A suggestive evidence of association was obtained for IL-10 592 C/A promoter polymorphism at the level of allele and genotype distribution. The frequency of IL-10 592 A allele and genotype was significantly increased in HSP compared to HSN (p = 0.013; OR = 1.412 and p = 0.034; OR = 1.685 respectively). Further comparison in between different clinical stages of HIV-1 infected patients of IL-10 592 A allele and genotype revealed a significant increase in its frequency in the stage III compared with those together in stage I (p = 0.004, OR = 2.181 and p = 0.002, OR = 4.156, respectively). This study reports for the first time that IL-10 gene promoter 592 C/A polymorphism may be a risk factor for HIV-1 transmission/progression in HIV-1 infected North Indian individuals.

摘要

引言

细胞因子在宿主免疫防御中发挥着重要作用。白细胞介素-10(IL-10)是一种抗炎、免疫调节细胞因子,既能刺激也能抑制免疫反应,并在体内抑制HIV-1复制。IL-10产生的个体差异在基因上归因于IL-10启动子区域内的多态性。

目的

本研究旨在调查IL-10基因启动子-1082G/A、-819C/T和592C/A多态性与北印度个体中HIV-1传播/进展的关联。

患者和方法

根据疾病严重程度(I、II和III期)对总共180名HIV-1血清阳性(HSP)患者、50名HIV-1暴露血清阴性(HES)个体和305名HIV-1血清阴性(HSN)个体进行分层,通过聚合酶链反应-限制性片段长度多态性对IL-10基因启动子进行基因分型。在等位基因和基因型分布水平上获得了IL-10 592C/A启动子多态性关联的提示性证据。与HSN相比,HSP中IL-10 592A等位基因和基因型的频率显著增加(分别为p = 0.013;OR = 1.412和p = 0.034;OR = 1.685)。对HIV-1感染患者不同临床阶段的IL-10 592A等位基因和基因型进行进一步比较,发现III期的频率与I期合并时相比显著增加(分别为p = 0.004,OR = 2.181和p = 0.002,OR = 4.156)。本研究首次报道,IL-10基因启动子592C/A多态性可能是HIV-1感染的北印度个体中HIV-1传播/进展的危险因素。

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