Impact of IL-6 and IL-6r variants on HIV-1 susceptibility and progression to AIDS: a case-control study in a Moroccan population

• Published in: Nucleosides, nucleotides & nucleic acids nucleotides & nucleic acids, 2024-09, Vol.43 (9), p.1045-1064
• Main Authors: Haddaji, Asmaa, Ouladlahsen, Ahd, Lkhider, Mustapha, Tanouti, Ikram-Allah, Abbadi, Islam, Hilmi, Soufiane, Bensghir, Rajaa, Guessous, Fadila, Pineau, Pascal, Marhoum El Filali, Kamal, Ezzikouri, Sayeh
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - genetics; Adult; AIDS; Antiretroviral therapy; Case-Control Studies; Cytokines; Disease Progression; Enzyme-linked immunosorbent assay; Female; Genetic Predisposition to Disease; Genotyping; Haplotypes; HIV; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - virology; HIV-1 - genetics; Human immunodeficiency virus; Humans; IL6; IL6R; Immune response; Infections; Inflammation; Interleukin 6; Interleukin-6 - genetics; Male; Middle Aged; Morocco; Polymorphism, Single Nucleotide; Population studies; Receptors, Interleukin-6 - genetics; Single-nucleotide polymorphism; variants
• ISSN: 1525-7770; 1532-2335; 1532-2335
• DOI: 10.1080/15257770.2024.2359593

Interleukin-6 (IL-6), a pro-inflammatory cytokine, is an important regulator of the inflammatory immune response. We aimed to assess the association of common single nucleotide polymorphisms (SNPs) in IL-6 (rs1800795 G > C, rs1800797 A > G) and interleukin-6 receptor (IL-6R) (rs2228145 A > C) genes with HIV-1 infection, AIDS progression, and response to treatment. In this case-control study involving 199 individuals living with HIV-1 and 200 HIV-uninfected controls, we conducted genotyping of IL-6/IL-6R SNPs using TaqMan real-time PCR assays. Soluble IL-6 levels were measured using ELISA. No associations were found between the investigated SNPs and HIV infection. However, a significant association was noted between the C-G and G-A haplotypes and susceptibility to HIV-1 infection. Additionally, a significant association was revealed between HIV-1 RNA viral loads and IL-6 SNP G > C in the post-treatment HIV group. Interestingly, we observed a significant association between the investigated SNPs and protection against progression to AIDS, namely the IL-6 G > A SNP in its recessive model and the IL-6R A > C SNP in its codominant and dominant models. Nevertheless, we found no significant differences between IL-6 levels and the different genotypes and alleles of the IL-6 gene either before or after combination antiretroviral therapy. IL-6 promoter haplotypes are associated with susceptibility to HIV-1 infection. Furthermore, IL-6 A > G and IL-6R A > C polymorphisms have been associated with protection against AIDS progression. Interestingly, the IL-6 G > C SNP may affect the response to treatment in people living with HIV-1.