Association between the MTNR1B, HHEX, SLC30A8, and TCF7L2 single nucleotide polymorphisms and cardiometabolic risk profile in a mixed ancestry South African population.

Single nucleotide polymorphisms of the TCF7L2, HHEX, SLC30A8, MTNR1B, SLC2A2 and GLIS3 genes are well established candidate genes for cardiometabolic diseases (CMDs) across different ethnic populations. We investigated their association with CMDs in a mixed ancestry population of South Africa. rs10830963, rs1111875, rs11920090, rs13266634, rs7034200 and rs7903146 SNPs were genotyped by quantitative real time PCR in 1650 participants and Hardy-Weinberg equilibrium (HWE) analyses performed on the SNPs. Diabetes, obesity, hypertension and cardiometabolic traits were compared across genotypes of SNPs in HWE. Linear and logistic regressions adjusting for age, gender and body mass index were used to determine the risk of T2DM, obesity and hypertension. rs7903146 (p = 0.055), rs1111875 (p = 0.465), rs13266634 (p = 0.828), and rs10830963 (p = 0.158) were in HWE. The rs10830963 recessive genotype was able to predict FPG, insulin and HOMA-IR, while the rs1111875 recessive genotype was able to predict total cholesterol, triglyceride, LDL cholesterol and FPG. The rs7903146 recessive genotype was able to predict SBP and LDL cholesterol. The recessive genotypes of MTNRIB and HHEX SNPs were associated with T2DM traits in the study population and could partially explain the high prevalence of T2DM. Further studies are required to confirm these findings and establish candidate genes in the African population.

Cardiometabolic profile and leukocyte telomere length in a Black South African population.

Several studies have reported a possible association between leucocyte telomere length (LTL) and cardio-metabolic diseases (CMDs). However, studies investigating such association are lacking in South Africa despite having a very high prevalence of CMDs. We investigated the association between LTL and CMD risk profile in a black South African population. This was a cross-sectional study with participants > 21 years of age and residing in five townships in Cape Town. CMD markers were compared between men and women and across quartiles of LTL. Linear and logistic regressions relate increasing quartile and Log10LTL with CMD risk profile, with appropriate adjustment. Among 676-participants, diabetes, obesity and hypertension prevalence were 11.5%, 23.1% and 47.5%. Waist-circumference, hip-circumference and highly sensitive c-reactive protein values were significantly higher in women (all p < 0.001), while HDL-C (p = 0.023), creatinine (p = 0.005) and gamma glutamyl transferase (p < 0.001) values were higher in men. In age, sex and BMI adjusted linear regression model, Log10 of LTL was associated with low HDL-C (beta = 0.221; p = 0.041) while logistic regression showed a significant association between Log10LTL and prevalent dyslipidaemia characterised by high LDL-C. In this population, the relationship between LTL and CMD is weak given its association with only HDL-C and LDL-C.

Associations of leucocyte telomere length with cardio-metabolic risk profile in a South African HIV-infected population.

ABSTRACT: Leukocyte Telomere length (LTL) is an independent predictor of cardio-metabolic diseases (CMDs) and Human Immuno Virus (HIV) infection. However, studies are lacking on the association between LTL with CMD profile in people with HIV. Accordingly, we investigated the association between LTL and CMD profile in HIV-infected adult South Africans.This cross-sectional study included 728 HIV patients (20.6% men; median age 38 years) recruited across 17 public healthcare facilities in Cape Town. CMD markers were compared across quartiles of LTL, and spearman correlations assessed the continuous association of LTL with CMD markers. Linear and logistic regressions were then used to relate LTL with CMD risk profile, with appropriate adjustment for confounders.The prevalence of obesity, hypertension and diabetes were 34.8%, 36.8%, and 8.4%, respectively. In age, sex and body mass index adjusted models, increasing Log10LTL was associated with decreasing systolic (ß = -10.52) and diastolic (ß = -6.74) blood pressures, HOMA-ß (ß = -70.72), increasing total cholesterol (ß = 0.544), non-high-density lipoprotein cholesterol (ß = 0.472), and waist-to-height-ratio > 0.5 (odds ratio [OR] = 5.67), all P < .05. Compared to those in the bottom quarter, those in the top LTL quarter had lower prevalence of hypertension (OR = 0.65), and higher prevalence of total cholesterol > 5 mmol/L (OR = 1.94), and low-density lipoprotein-cholesterol > 3 mmol/L (OR = 1.62), all P < .05. LTL was not associated with diabetes nor general obesity. It was associated with Alanine Transaminase (ALT) and heart rate in univariable analyses.LTL shortening was associated with some CMD risk factors in HIV-infected adults on anti-retroviral therapy in South Africa. Prospective research is needed to explore the direction and implications of these associations.