Genetic variations in human IL10 proximal promoter and Susceptibility to HIV infection: A pilot study in Mali, West Africa.

During the “Genetics of Infectious Diseases” session of the 12th Conference of the AfSHG and the 1st MSHG, Dr. Djeneba Dabitao, presented the topic: “Genetic variations in human IL10 proximal promoter and Susceptibility to HIV infection: A pilot study in Mali, West Africa”.

Background: Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that plays an important role in modulating immune responses in various conditions. Several reports have identified single nucleotide polymorphisms (SNPs) within the human /L10 proximal Promoter at position -1082 (G/A), -819 (C/T), and -592 (C/A). The SNPs form 3 common haplotypes: GCC, ACC and ATA in humans. The /L10 haplotypes have been associated with differential IL-10 expression and disease risk, mainly in Caucasians ar However, very little is known about their contribution to disease susceptibility such as HIV-1 in Africans populations, especially those living in West African region. Th we conducted a pilot study in Mali to determine whether /L10 SNPs haplotypes are associated with HIV-1 infection in a Malian population as a foundation for a larger population based study.

Methodology: One hundred and fifty-nine peripheral blood mononuclear cells were pooled from samples collected from an IRB-approved protocol of the SEREFO Laboratory at the University Clinical Research Center in Mali. Among these samples 71 (45%) were HIV positive and 88 (55%) were HIV negative. Genomic DNA was isolated using the Quiagen’s DNeasy Blood & Tissue kit and quantified using a Napodrop spectrophotometer. All DNA samples were then genotyped using the Taqman SNP genotyping assay on the ABI 75000.

Results and Conclusion: The -592 C/A, -819 C/T, and -1082 A/A alleles were the most represented in our study population, irrespective of the HIV status. Likewise the dominant haplotype was the ATA-low IL-10 producing haplotype (71%), followed by ACC (16%) and GCC ( 13%). Interestingly, we found a higher frequency of ATA/ATA carreers in HIV positive when compared to HIV negative, suggesting that the ATA-low IL-10 producing haplotype may increase susceptibility to HIV-1 infection. However, this
difference did not reach statistical significance (p: 0.26; OR: 1.63; CI of OR ( 0,73-3,68). Similar results were also found for the 2 other haplotypes. Therefore, we conclude that that the three IL10 SNPs haplotypes are not associated with HIV-1 susceptibility in our population, suggesting that other SNPs and or genes may be important for HIV-1 acquisition in Mali.

D Dabitao, M. Dembele, J. Bream, B. Kone, M. Wague, C. Nadie, YS Sarro, B. Baya, D. Goita, S. Dao’, R Murphy, WR. Bishai, S. Doumbia and S. Diallo.

° University Clinical Research Center (UCRC)

° Johns Hopkins University (JHU)

° National Institutes of Allergy and Infectious Diseases (NIAID)

° Northwestern University (NU)

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Ibrahima DIA

Communication Officer of the University Clinical Research Center (UCRC).

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