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HIV感染者中MMP-8基因多态性的患病率及其与HIV相关神经认知障碍的关联。

Prevalence of MMP-8 gene polymorphisms in HIV-infected individuals and its association with HIV-associated neurocognitive disorder.

作者信息

Singh HariOm, Samani Dharmesh, Nambiar Nayana, Ghate Manisha V, Gangakhedkar R R

机构信息

Department of Molecular Biology, National AIDS Research Institute, Pune 411026, India.

Department of Molecular Biology, National AIDS Research Institute, Pune 411026, India.

出版信息

Gene. 2018 Mar 10;646:83-90. doi: 10.1016/j.gene.2017.12.061. Epub 2017 Dec 29.

Abstract

Matrix metalloproteinases (MMPs) are well-known as mediators of neuroinflammation in HIV-associated neurocognitive disorder (HAND). Increased levels of MMP-8 have been observed in the HIV-infected patients. Thus, the aim of this study was to evaluate the association of MMP-8 gene polymorphisms with modulation of HAND severity and its prevalence in HIV-infected and healthy individuals. We enrolled a total of 150 HIV-infected individuals, 50 HAND patients, 100 HIV-infected and 150 healthy individuals. MMP-8 (-799C/T, +17C/G) polymorphisms were genotyped by PCR-RFLP. MMP-8 -799TT genotype and +17G allele showed the higher risk for modulation of HAND severity (OR=2.20, P=0.19; OR=1.97, P=0.23). MMP-8 -799TT genotype differed significantly in HIV-infected individuals compared to healthy controls (20.0% vs. 11.3%, OR=2.36, P=0.048). Haplotype TG increased the risk for modulation of HAND severity (OR=2.29, P=0.29). MMP-8 -799TT and +17CG genotypes were overrepresented in the intermediate HIV disease stage compared with healthy controls (25.9% vs. 11.3%, OR=4.34, P=0.021, 14.8% vs. 9.3%, OR=2.88, P=0.11). MMP-8 +17CG genotype enhanced the risk for modulation of HAND severity in tobacco using HAND patients (OR=5.01, P=0.17). MMP-8 -799TT genotype was more frequent in tobacco using HIV-infected individuals compared with nonusers (26.3% vs. 16.7%, OR=2.08, P=0.32). MMP-8 +17CG genotype increased the risk for modulation of HAND severity in alcohol using HAND patients (OR=4.99, P=0.18). In conclusion, MMP-8 polymorphisms independently and with alcohol and tobacco usage revealed a trend of higher risk for the modulation of HAND severity. MMP-8 -799TT genotype was associated with the advancement of HIV disease.

摘要

基质金属蛋白酶(MMPs)是众所周知的HIV相关神经认知障碍(HAND)中神经炎症的介质。在HIV感染患者中观察到MMP-8水平升高。因此,本研究的目的是评估MMP-8基因多态性与HAND严重程度调节及其在HIV感染个体和健康个体中的患病率之间的关联。我们共纳入了150名HIV感染个体、50名HAND患者、100名HIV感染个体和150名健康个体。通过PCR-RFLP对MMP-8(-799C/T,+17C/G)多态性进行基因分型。MMP-8 -799TT基因型和+17G等位基因显示出调节HAND严重程度的较高风险(OR=2.20,P=0.19;OR=1.97,P=0.23)。与健康对照相比,HIV感染个体中MMP-8 -799TT基因型有显著差异(20.0%对11.3%,OR=2.36,P=0.048)。单倍型TG增加了调节HAND严重程度的风险(OR=2.29,P=0.29)。与健康对照相比,MMP-8 -799TT和+17CG基因型在HIV疾病中期的比例过高(25.9%对11.3%,OR=4.34,P=0.021,14.8%对9.3%,OR=2.88,P=0.11)。MMP-8 +17CG基因型增加了使用烟草的HAND患者调节HAND严重程度的风险(OR=5.01,P=0.17)。与不使用烟草的HIV感染个体相比,使用烟草的HIV感染个体中MMP-8 -799TT基因型更常见(26.3%对16.7%,OR=2.08,P=0.32)。MMP-8 +17CG基因型增加了使用酒精的HAND患者调节HAND严重程度的风险(OR=4.99,P=0.18)。总之,MMP-8多态性独立地以及与酒精和烟草使用一起显示出调节HAND严重程度的较高风险趋势。MMP-8 -799TT基因型与HIV疾病进展相关。

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