Genetic Variants Linked to HIV-1 Exposure in Cameroonian Children and Adolescents and Their Association to Non-Communicable Diseases

Author(s): Béatrice Dambaya Ounzia, Georges Teto, Marcel Tongo, Laure Lemee, Elise Elong Lobe, Charlotte Tangimpundu, Guy Benoit Lekeufack, Céline Nguefeu Nkenfou, Flobert Njiokou, Vittorio Colizzi, Simon Eyongabane Ako and Alexis Ndjolo

Background: Children with HIV continue to be at a higher risk of non-communicable diseases (NCDs), even with improvements in the treatment of prenatal exposure to HIV-1 infection. This study aimed to identify genetic variations associated with HIV-1 and their potential influence on the risk of NCDs in offspring exposed during pregnancy.

Methods: We conduct a genome-wide association study (GWAS) on a cohort of 689 participants from Cameroon, employing a case-control design and a genomic epidemiology approach. Of these, 421 were HIV-infected and 268 were not. Single nucleotide polymorphisms (SNPs) were performed using Illumina BeadChips.

Results: Twenty SNPs in all were found, and the majority of the alterations were silent or synonymous. Those linked to HIV rapid progression include rs1422884 (GRIA1, Chr5) and exm665143 (TRPV6, Chr7) 7.9x10-6, with OR = 0.01, rs4915847 (C1orf87, Chr1), rs7578597, and exm189601 (THADA, Chr 2). The NCD-related SNPs rs1693687 (Chr10) 8.4x10-7 with OD=0.04 and rs7175885 (Chr15) showed significant associations with slow progression in HIV-infected individuals: THADA (rs7578597, exm189601, Chr2) was linked to type 2 diabetes and metabolic disorders. Both TENM2 (rs10057680, Chr5) and RBFOX1 (rs9302839, Chr16) have been associated with neurocognitive impairment. rs1693687 (Chr10) and rs10231785 (Chr7) were linked to cardiovascular diseases (CVDs). PHLPP1 (rs692916, Chr18) and ZNF208 (rs10426971, Chr19) have been connected to cancer risk and immune response.

Conclusion: The genetic variations linked to protective effects against HIV-1's rapid development as well as other variants with possible genetic resistance mechanisms are highlighted in this work. Additionally, several SNPs overlap with risk factors for NCDs, indicating that there may be common genetic processes. These results highlight the value of precision medicine strategies in HIV care.