Epidemiological correlates of overweight and obesity in the Northern Cape Province, South Africa.

Background: In the past several decades, obesity has become a major public health issue worldwide, associated with increased rates of chronic disease and death. Like many developing nations, South Africa is experiencing rapid increases in BMI, and as a result, evidence-based preventive strategies are needed to reduce the increasing burden of overweight and obesity. This study aimed to determine the prevalence and predictors of overweight and obesity among a multi-ethnic cohort from the rural Northern Cape of South Africa.

Different Selected Mechanisms Attenuated the Inhibitory Interaction of KIR2DL1 with C2 HLA-C in Two Indigenous Human Populations in Southern Africa.

The functions of human NK cells in defense against pathogens and placental development during reproduction are modulated by interactions of killer cell Ig-like receptors (KIRs) with HLA-A, -B and -C class I ligands. Both receptors and ligands are highly polymorphic and exhibit extensive differences between human populations. Indigenous to southern Africa are the KhoeSan, the most ancient group of modern human populations, who have highest genomic diversity worldwide.

An Unexpectedly Complex Architecture for Skin Pigmentation in Africans.

Approximately 15 genes have been directly associated with skin pigmentation variation in humans, leading to its characterization as a relatively simple trait. However, by assembling a global survey of quantitative skin pigmentation phenotypes, we demonstrate that pigmentation is more complex than previously assumed, with genetic architecture varying by latitude. We investigate polygenicity in the KhoeSan populations indigenous to southern Africa who have considerably lighter skin than equatorial Africans.

Structural and functional effects of nucleotide variation on the human TB drug metabolizing enzyme arylamine N-acetyltransferase 1.

The human arylamine N-acetyltransferase 1 (NAT1) enzyme plays a vital role in determining the duration of action of amine-containing drugs such as para-aminobenzoic acid (PABA) by influencing the balance between detoxification and metabolic activation of these drugs. Recently, four novel single nucleotide polymorphisms (SNPs) were identified within a South African mixed ancestry population. Modeling the effects of these SNPs within the structural protein was done to assess possible structure and function changes in the enzyme.

N-acetyltransferase genotypes and the pharmacokinetics and tolerability of para-aminosalicylic acid in patients with drug-resistant pulmonary tuberculosis.

The aim of this study was to examine the relationships between N-acetyltransferase genotypes, pharmacokinetics, and tolerability of granular slow-release para-aminosalicylic acid (GSR-PAS) in tuberculosis patients. The study was a randomized, two-period, open-label, crossover design wherein each patient received 4 g GSR-PAS twice daily or 8 g once daily alternately. The PAS concentration-time profiles were modeled by a one-compartment disposition model with three transit compartments in series to describe its absorption.

Acquired drug resistance during inadequate therapy in a young child with tuberculosis.

Drug resistance in children with tuberculosis is usually primary (transmitted); however, resistance acquisition during treatment is possible. We describe a child with tuberculosis who acquired drug resistance while receiving directly observed but inadequate first-line therapy and the programmatic and clinical factors that may have contributed to resistance acquisition.

Isoniazid pharmacokinetics, pharmacodynamics, and dosing in South African infants.

Aims: There are limited data on isoniazid (INH) pharmacokinetics in infants and young children and, therefore, uncertainty on appropriate dosing.

Methods: Pharmacokinetic data were obtained from perinatally HIV-exposed South African infants aged 3-24 months receiving INH 10-20 mg·kg·d orally for Mycobacterium tuberculosis prophylaxis. INH pharmacokinetic parameters were characterized using a population pharmacokinetic approach.

The pharmacogenetics of NAT2 enzyme maturation in perinatally HIV exposed infants receiving isoniazid.

The roles of the NAT2 genotype and enzyme maturation on isoniazid pharmacokinetics were investigated in South African infants with perinatal HIV exposure enrolled in a randomized, double-blind, controlled trial of isoniazid for prevention of tuberculosis disease and latent infection. Plasma concentration-time measurements of isoniazid from 151 infants (starting at 3-4 months of age) receiving isoniazid 10 to 20 mg/kg/d orally during the course of the 24-month study were incorporated in a population analysis along with NAT2 genotype, body weight, age, and sex. The results showed a different NAT2 enzyme maturation profile for each of the 3 acetylation groups, with the 70-kg body weight-normalized typical apparent clearance for the fast and intermediate acetylators increasing from 14.

Isoniazid plasma concentrations in a cohort of South African children with tuberculosis: implications for international pediatric dosing guidelines.

Background: In most countries with a high burden of tuberculosis, children with tuberculosis are prescribed isoniazid at dosages of 4-6 mg/kg/day, as recommended by international authorities.

Methods: We studied isoniazid concentrations in 56 hospitalized children (median age, 3.22 years; interquartile range [IQR], 1.

NAT2 polymorphisms and their influence on the pharmacology and toxicity of isoniazid in TB patients.

Tuberculosis is a global pandemic that threatens to overwhelm healthcare budgets in many developing countries. Despite the availability of adequate effective treatment, many patients default on treatment, experience adverse side effects from antibiotics or fail to respond rapidly and recover. Isoniazid, one of the most important first-line tuberculosis drugs, is acetylated in the liver to a variable degree in different individuals giving rise to fast, intermediate and slow acetylator phenotypes.

Allele frequencies for glutathione S-transferase and N-acetyltransferase 2 differ in African population groups and may be associated with oesophageal cancer or tuberculosis incidence.

Glutathione S-transferase (GST) and arylamine N-acetyltransferase 2 (NAT2) metabolise many environmental and chemotherapeutic agents, which influence susceptibility to disease. Polymorphisms in these enzymes result in different host phenotypes and contribute to different disease profiles or responses to toxic or chemotherapeutic agents, depending on their frequency in different populations. GST and NAT2 polymorphisms were investigated in different population groups, including African populations, and a range of allelic frequencies have been observed.

NAT2 slow acetylator function as a risk indicator for age-related cataract formation.

Objectives: To show that the slow arylamine N-acetyltransferase type 2 (NAT2) catalysed acetylator function is associated with the development of age-related cataracts.

Methods: Both the acetylator phenotype and genotype of 139 patients with age-related cataracts were determined, and the distribution of the acetylator subtypes in the case population was compared with the distribution in the general (control) population. The genotype was determined by restriction-enzyme analysis of DNA, and the phenotype was determined using the elimination characteristics of isoniazid as discriminant.