Virus restriction gene variants and their possible role in neurocognitive function in children born to HIV-infected mothers

Includes abstract.Includes bibliographical references.Host genetic variation is an important determinant of HIV infection, disease progression and HIV-associated neurocognitive deficits. However, there is no sufficient knowledge on the role of genetic variants especially among African populations. This study is focused on investigating variation in HIV/AIDS restriction genes; CCR2, CX3CR1, SDF1, RANTES, APOBEC3G and MBL2 and their possible role in HIV infection and neurocognitive function among children born to HIV infected mothers, recruited in Harare, Zimbabwe. A total of 116 children comprising of 73 perinatally exposed to HIV (34 who were born infected and 39 who were uninfected) and 43 unexposed controls were recruited in 2011(at ages 7-9 years) from a cohort of mother-baby pairs that has been followed up since 2002. The demographic characteristics of the recruited children were captured from their medical records. A McCarthy Scale of Children‟s Abilities (MSCA) was administered to determine each child‟s neurocognitive status. Genotyping for allelic variants was done using PCR-RFLP, SNaPshot® and Sanger DNA sequencing. Statistical analysis was carried out to determine association between genotypes, HIV status and neurocognitive function. The observation of different genetic variants or combinations of genotypes between the HIV-exposed and infected group and that of the HIV-exposed but uninfected group may be a pointer to critical pathways in differential HIV susceptibility. Exposure and infection with HIV is controlled by a multitude of genes/processes, thus, SNPs are unlikely to show statistically significant effects individually and may be more useful in a multifactorial model, as observed from comparisons of genotype combinations and haplotypes. The role of host genetic variation on neurocognitive function remains disputed but our observations suggest innate immune factors such as MBL2 may have a pronounced effect. Therefore, it may be possible to genotype for a suite of genes and use them as markers of either HIV susceptibility or neuro-developmental patterns