Dataset Information

Insights into the genetics of blood pressure in black South African individuals: the Birth to Twenty cohort.

ABSTRACT: BACKGROUND:Cardiovascular diseases (CVDs) are the leading cause of non-communicable disease deaths globally, with hypertension being a major risk factor contributing to CVDs. Blood pressure is a heritable trait, with relatively few genetic studies having been performed in Africans. This study aimed to identify genetic variants associated with variance in systolic (SBP) and diastolic (DBP) blood pressure in black South Africans. METHODS:Genotyping was performed using the Metabochip in a subset of participants (mixed sex; median age 17.9) and their adult female caregivers (median age 41.0) from the Birth to Twenty cohort (n?=?1947). Data were analysed as a merged dataset (all participants and caregivers together) in GEMMA (v0.94.1) using univariate linear mixed models, incorporating a centered relatedness matrix to account for the relatedness between individuals and with adjustments for age, sex, BMI and principal components of the genotype information. RESULTS:Association analysis identified regions of interest in the NOS1AP (DBP: rs112468105 - p?=?7.18?×?10-5 and SBP: rs4657181 - p?=?4.04?×?10-5), MYRF (SBP: rs11230796 - p?=?2.16?×?10-7, rs400075 - p?=?2.88?×?10-7) and POC1B (SBP: rs770373 - p?=?7.05?×?10-5, rs770374 - p?=?9.05?×?10-5) genes and some intergenic regions (DACH1|LOC440145 (DBP: rs17240498 - p?=?4.91?×?10-6 and SBP: rs17240498 - p?=?2.10?×?10-5) and INTS10|LPL (SBP: rs55830938 - p?=?1.30?×?10-5, rs73599609 - p?=?5.78?×?10-5, rs73667448 - p?=?6.86?×?10-5)). CONCLUSIONS:The study provided further insight into the contribution of genetic variants to blood pressure in black South Africans. Future functional and replication studies in larger samples are required to confirm the role of the identified loci in blood pressure regulation and whether or not these variants are African-specific.

SUBMITTER: Hendry LM

PROVIDER: S-EPMC5773038 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Insights into the genetics of blood pressure in black South African individuals: the Birth to Twenty cohort.

Hendry Liesl M LM Sahibdeen Venesa V Choudhury Ananyo A Norris Shane A SA Ramsay Michèle M Lombard Zané Z

BMC medical genomics 20180117 1

<h4>Background</h4>Cardiovascular diseases (CVDs) are the leading cause of non-communicable disease deaths globally, with hypertension being a major risk factor contributing to CVDs. Blood pressure is a heritable trait, with relatively few genetic studies having been performed in Africans. This study aimed to identify genetic variants associated with variance in systolic (SBP) and diastolic (DBP) blood pressure in black South Africans.<h4>Methods</h4>Genotyping was performed using the Metabochip ...[more]

PMID: 29343252

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Project description:Self-identified Black race is associated with higher hypertension prevalence and worse blood pressure (BP) control compared with other race/ethnic groups. The contribution of genetic West African ancestry to these racial disparities appears not to have been completely determined. To determine the association between the proportion of West African ancestry with the response to antihypertensive medication, BP control, kidney function, and risk of adverse cardiovascular (CV) events among self-identified Black individuals in the Systolic Blood Pressure Intervention Trial (SPRINT). This post hoc analysis of the SPRINT trial incorporated data from a multicenter study of self-identified Black participants with available West African ancestry proportion, estimated using 106 biallelic autosomal ancestry informative genetic markers. Recruitment started on October 20, 2010, and ended on August 20, 2015. Data were analyzed from May 2020 to September 2020. Trajectories of BP and kidney function parameters on follow-up of the trial were assessed across tertiles of the proportion of West African ancestry using linear mixed-effect modeling after adjustment for potential confounders. Multivariable adjusted Cox models evaluated the association of West African ancestry with the risk of composite CV events (nonfatal myocardial infarction, CV death, and heart failure event). Among 2466 participants in the current analysis (1122 women [45.5%]; median West African ancestry, 81% [interquartile range, 73%-87%]), there were 120 composite CV events (4.9%) over a mean (SD) of 3.2 (0.9) years of follow-up. At baseline, mean (SD) high-density lipoprotein cholesterol levels were higher (tertile 3: 56.5 [15.0] mg/dL vs tertile 1: 54.2 [14.9] mg/dL; P = .006), smoking prevalence (never smoking: tertile 3: 367 [47.9%] vs tertile 1: 372 [42.2%]; P = .009) and mean (SD) Framingham Risk scores (tertile 3: 16.7 [9.7] vs tertile 1: 18.1 [10.2]; P = .01) were lower, and baseline BP was not different across increasing tertiles of West African ancestry. On follow-up, there was no evidence of differences in longitudinal trajectories of BP, kidney function parameters, or left ventricular mass (Cornell voltage by electrocardiogram) across tertiles of West African ancestry in either intensive or standard treatment arms. In adjusted Cox models, higher West African ancestry was associated with a lower risk of a composite CV event after adjustment for potential confounders (adjusted hazard ratio per 5% higher West African ancestry, 0.92 [95% CI, 0.85-0.99]). Among self-reported Black individuals enrolled in SPRINT, the trajectories of BP, kidney function, and left ventricular mass over time were not different across tertiles of the proportion of West African ancestry. A higher proportion of West African ancestry was associated with a modestly lower risk for CV events. These findings suggest that extrinsic and structural societal factors, more than genetic ancestry, may be the major drivers of the well-established racial disparity in cardiovascular health associated with hypertension.

Project description:An intronic single nucleotide polymorphism (SNP) in RICH2 (rs2072255; 255i), in complete linkage disequilibrium (LD) with an exonic SNP (rs2072254; 254e), has been identified in a genome wide association study to be associated with progression to AIDS in Caucasian individuals. RICH2 links tetherin to the cortical actin network and the RICH2/tetherin interaction has been shown to be important for the downstream activation of NF-κβ and the consequential promotion of proinflammatory responses. We investigated the role of these two SNPs in natural control of HIV-1 in black South Africans including healthy controls (HCs; N=102) and antiretroviral-naive HIV-1-infected controllers (HICs; N=52) and progressors (N=74). HICs were stratified as elite controllers (ECs; N=11), viraemic controllers (VCs; N=30), high viral load (VL) long term non-progressors (HVL LTNPs; N=11) and also according to VL<400RNA copies/ml (HICs VL<400; N=20) and VL>400RNA copies/ml (HICs VL>400; N=32). Results showed that in contrast to Caucasians who had very strong LD between these SNPs (r2=0.97), black populations exhibited low LD (r2=0.11-0.27), however a 254e minor allele was always present with a 255i minor allele but not vice versa. The SNPs did not show significant over- or underrepresentation in any particular group, however the combination of 254e major allele homozygosity and 255i heterozygosity (254eAA/255iGA) was underrepresented in HICs (OR=3.26; P=0.04) and VCs (OR=7.77; P=0.02) compared to HCs, and in HICs VL>400 compared to both HCs (P=0.002) and progressors (P=0.02). A lower CD4+ T-cell count was associated with 254eAA/255iGA and 255i (GA+AA) in the total HIV-1-infected group (P=0.043) and progressors (P=0.017), respectively. In silico analysis predicted loss of an exonic splice enhancer site with the 254e-G allele. We postulate that altered splicing of RICH2 will affect levels of RICH2 expression and consequently NF-κβ activation. These findings point to a role for RICH2 and tetherin in viraemic natural control of HIV-1.

Project description:BACKGROUND:To report associations between different adiposity indices [anthropometric and dual-energy X-ray absorptiometry (DXA) measures] and blood pressure (BP) and hypertension in urban black South African adults. METHODS:Anthropometric and DXA whole body measures were performed on 1026 men and 982 women. Participants were classified as being hypertensive if they had a systolic BP (SBP)???140 mmHg and/or diastolic (DBP)???90 mmHg. Within each gender the relationship of adiposity with BP and hypertension risk was assessed using linear and logistic regression models respectively. Bivariate models were computed for each body composition variable. Furthermore, we computed a multiple regression model to illustrates how body composition parameters are associated with the outcome variables independent of each other. RESULTS:The males were significantly taller and had a higher fat free soft tissue mass (FFSTM), DBP and socio-economic status, and were more likely to use tobacco and be hypertensive (48.0% vs. 38.8%). The females had higher body mass index (BMI), waist circumference (WC), fat mass (FM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), FM/FFSTM ratio and body fat % than males. All body composition parameters were positively associated with hypertension. In both males and females, the FM/FFSTM ratio associated the strongest with hypertension illustrating the following odds ratios [males: 70.37 (18.47, 268.16) p ??0.001; females 2.48 (0.86,7.21) p =?0.09]. The multiple regression model, indicated that the VAT and WC significantly associated with both SBP and DBP in the men and women respectively, whilst WC was the only significant predictor for hypertension. CONCLUSIONS:All body composition parameters were associated with hypertension and FM/FFSTM ratio showed the strongest relationship. It was reassuring that WC remains a useful measure of central adiposity that can be used as a risk indicator for hypertension if more sophisticated measures are not available. Furthermore, our data in part, implies that reducing abdominal adiposity in aging adults could contribute to reducing the risk of elevated blood pressure and hypertension.

Dataset Information

Insights into the genetics of blood pressure in black South African individuals: the Birth to Twenty cohort.

Publications

Insights into the genetics of blood pressure in black South African individuals: the Birth to Twenty cohort.

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