Interleukin-10 Promoter Polymorphisms Influence HIV-1 Susceptibility and Primary HIV-1 Pathogenesis

Hasso Plattner Research Laboratory, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
The Journal of Infectious Diseases (Impact Factor: 5.78). 07/2009; 200(3):448-52. DOI: 10.1086/600072
Source: PubMed

ABSTRACT Interleukin (IL)-10 directly inhibits human immunodeficiency virus type 1 (HIV-1) replication, but it may also promote viral persistence by inactivation of effector immune mechanisms. Here, we show in an African cohort that individuals with genotypes associated with high IL-10 production at 2 promoter single-nucleotide polymorphisms (-1082 and -592) were less likely to become HIV-1 infected but had significantly higher median plasma viral loads during the acute phase (<or=3 months after infection). However, as the infection progressed, the association between genotype and median viral load was reversed. Thus, IL-10 may influence HIV-1 susceptibility and pathogenesis, but effects on the latter may differ according to the infection phase.

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    ABSTRACT: Background & Objective: Interleukin (IL)-10 is an important anti-inflammatory and immunomodulatory cytokine. Some authors believe that single nucleotide polymorphisms (SNP) in the promoter region of the IL-10 gene have been associated with susceptibility to HIV infection and progression to AIDS, but its role is not clearly defined yet. The present study was undertaken to evaluate the association between HIV infection susceptibility and progression with SNP in the promoter region of the IL-10 gene. Methods: This study was carried out on 70 HIV infected patients (39 treatment naïve and 31under treatment) and 31 matched healthy controls. The biallelic polymorphisms in the IL-10 gene promoter (-592 ,-1082) were analyzed by polymerase chain reaction and direct sequencing. Results: At position -1082, G/A was the most common genotype and A was the most prevalent allele and at position -592, A/C was the most prevalent genotype and -592 C was the most common allele in HIV positive patients; although there was not any significant difference between cases and controls regarding genotypes and alleles of these regions. Conclusion: Genetic polymorphisms of IL-10 promoter region may not associate with HIV infection outcome and the lack of this association suggests that other genes may influence on HIV infection course.
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    ABSTRACT: Interleukin 10 (IL-10) is a multifunctional cytokine produced by macrophages, monocytes, and T-helper cells. Two polymorphisms at positions -592 and -1082 have been associated with HIV susceptibility. However, their associations with susceptibility to HIV and its co-infections among intravenous drug users (IDUs) are largely unknown. A total of 345 IDUs were recruited. Of the 173 HIV negative IDUs, 20 were classified as highly exposed HIV seronegative subjects (HESNs). A control group consisted of 496 blood donors; all HIV, HCV, and HBV negative. The IL-10 -592C/A and -1082A/G were determined using TaqMan allelic discrimination assay. Of the IDUs, 50% were HIV positive, 89% HCV positive, 67% HBV positive and 41% had triple infection. IL-10 -592C allele and -1082A allele were the most common and the -1082 AG/-592CC was the most common genotype pair. All HESNs exhibited -1082A allele as compared to 81.4% of the HIV positive IDUs and 79% of donors (p=0.029 and p=0.019, respectively). None of HESNs had GG/CC genotype pair compared with 18.6% of HIV+ IDUs and 21.0% of donors (p=0.029 and p=0.019, respectively). The possession of -592AC and genotype pair AG/AC were associated with the decreased odds of HBV infection (OR=0.28; 95% CI 0.09-0.87; p=0.028 and OR=0.19; 95% CI 0.06-0.61; p=0.052, respectively). The presence of low producing IL-10 -1082A and -592A alleles and their containing genetic variants protect highly exposed IDUs against acquisition of HIV and HBV infections. Copyright © 2014. Published by Elsevier B.V.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 12/2014; DOI:10.1016/j.meegid.2014.12.023 · 3.26 Impact Factor
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