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rs1799750 的 1G/1G+1G/2G 基因型与更高水平的 MMP-1 相关,并且均与接受抗逆转录病毒治疗的 HIV 感染者的脂肪营养不良相关。

The 1G/1G+1G/2G Genotypes of rs1799750 Are Associated with Higher Levels of MMP-1 and Are Both Associated with Lipodystrophy in People Living with HIV on Antiretroviral Therapy.

机构信息

Faculty of Medical Sciences (FCM), University of Pernambuco (UPE), Recife, Brazil.

Instituto Aggeu Magalhães (IAM), Oswaldo Cruz Foundation (FIOCRUZ), Recife, Brazil.

出版信息

AIDS Res Hum Retroviruses. 2021 May;37(5):399-406. doi: 10.1089/AID.2020.0237. Epub 2021 Mar 22.

DOI:10.1089/AID.2020.0237
PMID:33587019
Abstract

In HIV-infected patients, antiretroviral therapy (ART) is associated to adipose tissue redistribution known as lipodystrophy (LD). This study aimed at verifying the association between the polymorphism of the gene (rs1799750) (1G/2G) and the serum levels of matrix metalloproteinase 1 (MMP-1) with LD and its subtypes in people living with HIV on ART. This is a cross-secional study. LD was self-reported. The determination of the rs1799750 gene polymorphism was performed by real-time PCR, and the serum concentrations of MMP-1 were quantified by the enzyme-linked immunosorbent assay (ELISA) method. Of 404 participants, 204 (51%) were diagnosed with LD, of whom 89 (43%) had mixed lipodystrophy (ML), 72 (35%) had lipohypertrophy (LH), and 43 (22%) had lipoatrophy (LA). There was an association between the genotypes 1G/1G+1G/2G and higher serum levels of MMP-1 ( = .025). There was no association of (1G/2G) with LD. Other factors associated with LD were current CD4 ≤ 350 [odds ratio (OR) = 4.85, confidence interval (CI) = 1.78-47.99,  = .0033] and serum MMP-1 levels >6.81 (OR = 2.67, CI = 1.21-6.08,  = .0165). Factors associated with ML: current CD4 ≤ 350 (OR = 5.59, CI = 1.69-20.39,  = .006); with LH: number of antiretroviral regimens used: 2 (OR = 2.06, CI = 1.01-4.20,  = .0460) and 3+ (OR = 2.09, CI = 1.00-4.35,  = .0477), and current CD4 ≤ 350 (OR = 2.08, CI = 1.00-4.24,  = .0461); and with LA: current viral load >40 (OR = 2.52, CI = 1.03-5.91,  = .0372) and current use of zidovudine (OR = 2.97, CI = 1.32-6.54,  = .0074). Higher levels of MMP-1 were associated with genotypes 1G/2G+1G/1G and with LD. Other individual risk factors were independently associated with LD, and its subtypes, suggesting that the pathogenesis itself is differently manifested for each type of LD.

摘要

在感染 HIV 的患者中,抗逆转录病毒治疗 (ART) 与脂肪组织重新分布有关,称为脂肪营养不良 (LD)。本研究旨在验证基因 (rs1799750) (1G/2G) 多态性与血清基质金属蛋白酶 1 (MMP-1) 水平与接受 ART 的 HIV 感染者 LD 及其亚型之间的关系。这是一项横断面研究。LD 通过自我报告进行诊断。通过实时 PCR 进行 rs1799750 基因多态性的测定,通过酶联免疫吸附测定 (ELISA) 方法定量 MMP-1 的血清浓度。在 404 名参与者中,204 名 (51%) 被诊断为 LD,其中 89 名 (43%) 患有混合性脂肪营养不良 (ML),72 名 (35%) 患有脂肪肥大 (LH),43 名 (22%) 患有脂肪萎缩 (LA)。基因型 1G/1G+1G/2G 与较高的 MMP-1 血清水平有关 (=.025)。与 LD 没有关联。与 LD 相关的其他因素包括当前 CD4≤350[比值比 (OR) = 4.85,置信区间 (CI) = 1.78-47.99,= .0033]和血清 MMP-1 水平 >6.81(OR = 2.67,CI = 1.21-6.08,= .0165)。与 ML 相关的因素:当前 CD4≤350(OR = 5.59,CI = 1.69-20.39,= .006);与 LH 相关的因素:抗逆转录病毒方案的使用数量:2(OR = 2.06,CI = 1.01-4.20,= .0460)和 3+(OR = 2.09,CI = 1.00-4.35,= .0477),以及当前 CD4≤350(OR = 2.08,CI = 1.00-4.24,= .0461);与 LA 相关的因素:当前病毒载量 >40(OR = 2.52,CI = 1.03-5.91,= .0372)和当前使用齐多夫定(OR = 2.97,CI = 1.32-6.54,= .0074)。较高的 MMP-1 水平与基因型 1G/2G+1G/1G 有关,与 LD 有关。其他个体危险因素与 LD 及其亚型独立相关,提示每种类型的 LD 的发病机制表现不同。

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