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MBL2 gene polymorphisms in HHV-8 infection in people living with HIV/AIDS
Retrovirology ( IF 2.7 ) Pub Date : 2018-11-27 , DOI: 10.1186/s12977-018-0456-8
Viviane Martha Santos de Morais , Elker Lene Santos de Lima , Georgea Gertrudes de Oliveira Mende Cahú , Thaisa Regina Rocha Lopes , Juliana Prado Gonçales , Maria Tereza Cartaxo Muniz , Maria Rosângela Cunha Duarte Coêlho

BackgroundHost genetic factors such as MBL2 gene polymorphisms cause defects in the polymerization of MBL protein and result in a functional deficiency and/or in low serum levels that can influence susceptibility to various viral infections. The aim of this study was to estimate the frequency of alleles, genotypes and haplotypes related to -550, -221 and exon 1 polymorphisms of the MBL2 gene and investigate their association with HHV-8 in people living with HIV/AIDS (PLWHA), as well as the impacts on CD4 cell count and HIV viral load in HIV/HHV-8 coinfected and HIV monoinfected patients.ResultsA cross sectional study in PLWHA, with and without HHV-8 infection, exploring associations between different factors, was performed in the outpatient infectious and parasitic diseases clinic at a referral hospital. Genomic DNA extractions from leukocytes were performed using a commercial Wizard®Genomic DNA Purification kit (Promega, Madison, WI). The promoter region (-550 and -221) was genotyped with the TaqMan system (Applied TaqMan Biosystems® genotyping Assays), and the structural region (exon1) was genotyped with Express Sybr Greener Supermix kit (Invitrogen, USA). In total, 124 HIV/HHV-8 coinfected and 213 HIV monoinfected patients were analysed. Median TCD4 counts were significantly lower in HIV/HHV-8 coinfected patients, whereas the mean of the first and last viral load of HIV did not present significant difference. There was no difference in frequency between the LL, YY and AA genotypes between the HIV/HHV-8 coinfected or HIV monoinfected patients. However, in a multivariate analysis, coinfected patients with the intermediate expression haplotype of the MBL2 gene had an odds ratio of 3.1-fold (CI = 1.2–7.6) of their last CD4 cell count being below 350 cells/mm3. Among the coinfected individuals, four developed KS and presented the intermediate expression MBL haplotype, with three being HYA/LXA and one being LYA/LYO.ConclusionsHost genetic factors, such as -550, -221 and exon 1 polymorphisms, can be related to the may modify coinfections and/or to the development clinical manifestations caused by HHV-8, especially in HIV/HHV-8 coinfected patients who present the intermediate expression haplotypes of MBL.

中文翻译:

HIV/AIDS患者HHV-8感染中的MBL2基因多态性

背景宿主遗传因素如 MBL2 基因多态性导致 MBL 蛋白聚合缺陷并导致功能缺陷和/或低血清水平,从而影响对各种病毒感染的易感性。本研究的目的是估计与 MBL2 基因的 -550、-221 和外显子 1 多态性相关的等位基因、基因型和单倍型的频率,并调查它们与 HIV/AIDS 患者 (PLWHA) 中 HHV-8 的关联,以及对 HIV/HHV-8 合并感染和 HIV 单一感染患者的 CD4 细胞计数和 HIV 病毒载量的影响。结果 在有和没有 HHV-8 感染的 PLWHA 中进行横断面研究,探索不同因素之间的关联,在转诊医院的传染病和寄生虫病门诊。从白细胞中提取基因组 DNA 使用商业 Wizard®基因组 DNA 纯化试剂盒(Promega,麦迪逊,威斯康星州)进行。启动子区域(-550 和 -221)使用 TaqMan 系统(Applied TaqMan Biosystems® 基因分型分析)进行基因分型,结构区域(外显子 1)使用 Express Sybr Greener Supermix 试剂盒(Invitrogen,美国)进行基因分型。总共分析了 124 名 HIV/HHV-8 合并感染和 213 名 HIV 单一感染患者。HIV/HHV-8 共感染患者的 TCD4 计数中位数显着较低,而 HIV 的第一次和最后一次病毒载量的平均值没有显着差异。HIV/HHV-8 合并感染或 HIV 单一感染患者的 LL、YY 和 AA 基因型之间的频率没有差异。然而,在多元分析中,具有 MBL2 基因中间表达单倍型的共感染患者最后一次 CD4 细胞计数低于 350 个细胞/mm3 的比值比为 3.1 倍(CI = 1.2-7.6)。在共感染个体中,4个发展为KS并呈现中间表达MBL单倍型,其中3个为HYA/LXA,1个为LYA/LYO。结论宿主遗传因素,如-550、-221和外显子1多态性,可能与可能会改变由 HHV-8 引起的合并感染和/或发展临床表现,特别是在呈现 MBL 中间表达单倍型的 HIV/HHV-8 合并感染患者中。
更新日期:2018-11-27
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