Characterization of CYP2B6 and CYP2A6 Pharmacogenetic Variation in Sub-Saharan African Populations.

Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub-Saharan African (SSA) populations.

Characterization of CYP2D6 Pharmacogenetic Variation in Sub-Saharan African Populations.

Cytochrome P450 2D6 (CYP2D6) is a key enzyme in drug response owing to its involvement in the metabolism of ~ 25% of clinically prescribed medications. The encoding CYP2D6 gene is highly polymorphic, and many pharmacogenetics studies have been performed worldwide to investigate the distribution of CYP2D6 star alleles (haplotypes); however, African populations have been relatively understudied to date. In this study, the distributions of CYP2D6 star alleles and predicted drug metabolizer phenotypes-derived from activity scores-were examined across multiple sub-Saharan African populations based on bioinformatics analysis of 961 high-depth whole genome sequences.

FCGR3A gene duplication, FcγRIIb-232TT and FcγRIIIb-HNA1a associate with an increased risk of vertical acquisition of HIV-1.

Background: Some mother-to-child transmission (MTCT) studies suggest that allelic variations of Fc gamma receptors (FcγR) play a role in infant HIV-1 acquisition, but findings are inconsistent. To address the limitations of previous studies, the present study investigates the association between perinatal HIV-1 transmission and FcγR variability in three cohorts of South African infants born to women living with HIV-1.

Methods: This nested case-control study combines FCGR genotypic data from three perinatal cohorts at two hospitals in Johannesburg, South Africa.

Reduced CCR5 Expression and Immune Quiescence in Black South African HIV-1 Controllers.

Unique Individuals who exhibit either suppressive HIV-1 control, or the ability to maintain low viral load set-points and preserve their CD4+ T cell counts for extended time periods in the absence of antiretroviral therapy, are broadly termed HIV-1 controllers. We assessed the extent to which black South African controllers (n=9), differ from uninfected healthy controls (HCs, n=22) in terms of lymphocyte and monocyte CCR5 expression (density and frequency of CCR5-expressing cells), immune activation as well as peripheral blood mononuclear cell (PBMC) mitogen-induced chemokine/cytokine production. In addition, relative CD4+ T cell CCR5 mRNA expression was assessed in a larger group of controllers (n=20) compared to HCs (n=10) and HIV-1 progressors (n=12).

An HIV Vaccine Protective Allele in Associates With Increased Odds of Perinatal HIV Acquisition.

In the Thai RV144 HIV-1 vaccine trial, a three-variant haplotype within the Fc gamma receptor 2C gene () reduced the risk of HIV-1 acquisition. A follow-on trial, HVTN702, of a similar vaccine candidate found no efficacy in South Africa, where the predominant population is polymorphic for only a single variant in the haplotype, c.134-96C>T (rs114945036).