Prevalence of MMP-8 gene polymorphisms in HIV-infected individuals and its association with HIV-associated neurocognitive disorder
Prevalence of MMP-8 gene polymorphisms in HIV-infected individuals and its association with HIV-associated neurocognitive disorder
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DOI：
10.1016/j.gene.2017.12.061
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发表时间：
2018-03-10
期刊：
影响因子：
3.5
通讯作者：
Gangakhedkar, R. R.
中科院分区：
文献类型：
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作者：
Singh, HariOm;Samani, Dharmesh;Gangakhedkar, R. R.
基质金属蛋白酶(MMPs)是HIV相关性神经认知障碍(HAND)中神经炎症的介质。在HIV感染患者中观察到了基质金属蛋白酶-8水平的升高。因此，这项研究的目的是评估基质金属蛋白酶-8基因多态性与手部严重程度的调节及其在HIV感染和健康个体中的流行之间的关系。我们共招募了150名艾滋病毒感染者、50名手部患者、100名艾滋病毒感染者和150名健康人。采用聚合酶链式反应-限制性片段长度多态性分析技术检测基质金属蛋白酶-8(-799C/T，+17C/G)基因多态性。MMP8-799TT和+17G等位基因与手部严重程度相关(OR=2.20，P=0.19；OR=1.97，P=0.23)。HIV感染者MMP8-799TT型与健康对照组比较差异有统计学意义(20.0%vs.11.3%，OR=2.36，P=0.048)。单倍型TG增加了调节手部严重程度的风险(OR=2.29，P=0.29)。MMP8-799TT型和+17CG型在HIV疾病中期组中的阳性率分别为25.9%和14.8%，显著高于健康对照组的11.3%(OR=4.34，P=0.021)和9.3%。MMP8+17CG基因型增加了吸烟者手部严重程度调整的风险(OR=5.01，P=0.17)。在吸烟的HIV感染者中，MMP8-799TT基因型的频率高于非吸烟者(26.3%vs.16.7%，OR=2.08，P=0.32)。MMP8+17CG基因型增加了饮酒后手部严重程度改变的风险(OR=4.99，P=0.18)。综上所述，基质金属蛋白酶-8基因的多态与饮酒和吸烟无关，显示出调节手部严重程度的风险更高的趋势。MMP8-799TT基因与HIV疾病的进展相关。
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.