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白细胞介素-10 启动子的遗传变异影响波兰人群中 HIV-1 感染和疾病进展的易感性:白细胞介素-10 多态性与 HIV-1。

Genetic variants of IL-10 promoter influence susceptibility to HIV-1 infection and disease progression in the Polish population: IL-10 polymorphisms and HIV-1.

机构信息

Department of Microbiology and Virology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, ul. Jagiellońska 4, Poland.

Department of Medical Microbiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, 40-752 Katowice, ul. Medyków 18, Poland.

出版信息

Hum Immunol. 2024 Sep;85(5):111086. doi: 10.1016/j.humimm.2024.111086. Epub 2024 Aug 16.

DOI:10.1016/j.humimm.2024.111086
PMID:39153369
Abstract

The risk of HIV-1 infection and the rate of disease progression vary considerably among individuals and the genetic makeup of the host may be one of the possible reasons for this. We aimed to determine association of functional single nucleotide polymorphism (SNPs), -1082A/G (rs1800896), -819C/T (rs1800871), and -592C/A (rs1800872) in IL-10 gene, with the susceptibility to HIV-1 infection and clinical parameters expressed as a baseline CD4 T cell count, CD8 T cell count, and viral load. Therapy naïve HIV-1 infected individuals and HIV-1 seronegative controls from Poland were recruited for this study. Genotyping results revealed significantly higher frequency of -1082G/G genotype (28.1 % vs 16.1 %; p = 0.0019, OR=0.49) and -1082G allele (47.6 % vs 38.8 %; p = 0.0028, OR = 0.70) as well as lower frequency of -592 and -819 heterozygosity (45.0 % vs 34.4 %; p = 0.0266, OR = 1.47) in controls compared to seropositive subjects. High producing haplotype GCC was associated with increased risk of HIV-1 infection (p = 0.0018, OR = 1.52). Individuals possessing -592 and -819 minor allele had significantly higher CD8 T cell count compared to the wild type allele carriers (p = 0.0303). Moreover, presence of -1082G allele was related with lower viral load as well as CD4 and CD8 T cells counts among patients infected with R5 HIV-1 variant. Thus, IL-10 gene promoter variants may be a risk factor for HIV-1 transmission and may modulate disease progression in the Polish population.

摘要

HIV-1 感染的风险和疾病进展的速度在个体之间有很大的差异,宿主的遗传构成可能是其中的一个可能原因。我们旨在确定白细胞介素 10 基因中的功能性单核苷酸多态性(SNP)-1082A/G(rs1800896)、-819C/T(rs1800871)和-592C/A(rs1800872)与 HIV-1 感染易感性以及临床参数(表现为基线 CD4 T 细胞计数、CD8 T 细胞计数和病毒载量)之间的关联。本研究招募了来自波兰的未经治疗的 HIV-1 感染个体和 HIV-1 血清阴性对照者。基因分型结果显示,-1082G/G 基因型(28.1%比 16.1%;p=0.0019,OR=0.49)和-1082G 等位基因(47.6%比 38.8%;p=0.0028,OR=0.70)的频率显著升高,而-592 和-819 杂合性的频率(45.0%比 34.4%;p=0.0266,OR=1.47)在对照组中也低于血清阳性者。高产生的 GCC 单倍型与 HIV-1 感染的风险增加相关(p=0.0018,OR=1.52)。与野生型等位基因携带者相比,携带-592 和-819 次要等位基因的个体的 CD8 T 细胞计数显著升高(p=0.0303)。此外,-1082G 等位基因的存在与 HIV-1 R5 变异体感染患者的病毒载量以及 CD4 和 CD8 T 细胞计数较低有关。因此,白细胞介素 10 基因启动子变异可能是 HIV-1 传播的危险因素,并可能在波兰人群中调节疾病进展。

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