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Association of CD209 promoter variants and tuberculosis infection susceptibility, AIDS development, and treatment response outcomes among the HIV-1 Moroccan population

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Abstract

The DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) molecules located on the surface of Dendritic Cell subsets showed high-affinity binding to HIV-1 and Mycobacterium tuberculosis (Mtb). It is exploited by HIV-1 and Mtb as a part of their immune evasion strategy. In this study, we explored how variations in the CD209 gene, which encodes for DC-SIGN, may be linked to the development of tuberculosis (TB) in individuals with HIV-1 infection. Additionally, we examined their potential association with the progression of AIDS and the treatment response outcome in the Moroccan population.Two single nucleotide polymorphisms in the CD209 promoter − 336A>G (rs4804803) and − 139G>A (rs2287886) were investigated. Two hundred eighteen Moroccan patients living with HIV-1 were genotyped using direct DNA sequencing. Among the 218 patients, 90 were found to have a co-infection with Mtb. We categorized the patients based on their TB status into two groups: those with HIV-1 infection and without TB (HIV-1+/TB−) and those with both HIV-1 infection and TB (HIV-1+/TB+). We further classified them based on their AIDS status into two groups: AIDS and Non-AIDS patients.Our results revealed that genotype and allele frequencies of the − 336A>G and − 139G>A polymorphisms were not significantly different between HIV-1+/TB− and HIV-1+/TB+ patients (p > 0.05). Likewise, the development of AIDS does not appear to be affected by these two SNPs either (p > 0.05). Haplotype analysis showed that none of the 4 possible haplotypes is associated with HIV-1 and TB co-infection (p > 0.05). Interestingly, the analysis of the − 139G>A genotype distribution according to the HIV-1 viral load showed an improvement in patients with AG and GG genotypes, after antiretroviral therapy, compared to AA patients (p = 0.0069 and p = 0.0476; respectively). Overall, − 336A>G and − 139G>A polymorphisms do not influence the susceptibility of HIV-1-infected individuals to develop TB and AIDS. However, − 139G>A polymorphism may affect the response to treatment as measured by RNA viral load levels.

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Acknowledgements

The authors are deeply indebted to all subjects for their participation in this study. The study was supported by Institut Pasteur du Maroc. We are particularly grateful and have a great honor to have worked with the deceased FAYSSEL Naouar Ph.D.

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Author notes

  1. Deceased: Naouar Fayssel.

Authors and Affiliations

  1. Immuno-Virology Laboratory, Virology Unit, Institut Pasteur du Maroc, Casablanca, Morocco

    Hanâ Baba, Naouar Fayssel, Meryem Bouqdayr, Laila Amar, Asmae Saih & Lahcen Wakrim

  2. Laboratory of Biology and Health, URAC 34, Faculty of Sciences Ben M’Sik, Hassan II University-Casablanca, Casablanca, Morocco

    Hanâ Baba, Meryem Bouqdayr, Asmae Saih & Anass Kettani

  3. Service Des Maladies Infectieuses, CHU Ibn Rochd, Casablanca, Morocco

    Ahd Ouladlahsen, Rajaa Bensghir, Latifa Marih, Mustapha Sodqi & Kamal Marhoum El Filali

  4. Viral Hepatitis Laboratory, Virology Unit, Institut Pasteur du Maroc, Casablanca, Morocco

    Imane Zaidane

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  1. Hanâ Baba
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Contributions

HB wrote the manuscript, HB, NF and LW conceived and designed the experiments, HB andd LA performed experiments, RB and AO, MS and LM helped in sample collection; KMEF and AO contributed the clinical data; ASMB helped in the statistical analysis and the interpretation of data, IZ facilitated drafting editing, AK and LW did final editing. All authors discussed the results and contributed to the final manuscript, and consented to publish.

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Correspondence to Hanâ Baba.

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The authors declare that they have no conflicts of interest to disclose.

Ethical approval and informed consent

This study was conducted in adherence to ethical standards and guidelines. All human research participants were treated in accordance with the principles outlined in the 1975 Declaration of Helsinki for human research. Ethical approval for this study was granted by the biomedical research at Mohammed V University at Rabat, Morocco with the given registration number N°24/18. Informed consent was obtained from all human participants, and all personal information was handled in compliance with data protection regulations. Privacy and confidentiality were rigorously maintained, and all data were de-identified and analyzed anonymously.

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Corresponding Editor: Sandipan Brahma; Reviewer: Elizabeth Ryan.

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Baba, H., Fayssel, N., Bouqdayr, M. et al. Association of CD209 promoter variants and tuberculosis infection susceptibility, AIDS development, and treatment response outcomes among the HIV-1 Moroccan population. Nucleus (2023). https://doi.org/10.1007/s13237-023-00453-3

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