Genetic factors contributing to hypertension in African-based populations: A systematic review and meta-analysis.
Ontology highlight
ABSTRACT:
SUBMITTER: Yako YY
PROVIDER: S-EPMC8031059 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Identification of genetic/genomic factors contributing to dyslipidemia is of great interest to prevention and reduction of the onset and burden of cardiovascular diseases in Africa. This systematic review summarizes available data on genetic variants associated with dyslipidemia in populations within Africa. A PubMed and EMBASE database search was conducted to identify all studies published until June 2018 on genetic susceptibility to dyslipidemia in African-based populations, excluding familial hypercholesterolemia. All studies on genetic predispositions of dyslipidemia and respecting the preestablished inclusion criteria were included in this systematic review. Because of high heterogeneity, the data were summarized narratively. Twenty-two studies investigated mostly the targeted genetic variants. A total of 51 polymorphisms in 28 susceptibility genes to dyslipidemia have been associated with a particular trait in the African populations, and through variable effects. Most polymorphisms investigated in Northern Africa seemed to have consistent effects on increasing the level of low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides in patients with diabetes, myocardial infarction, coronary artery disease, and metabolic syndrome. By contrast, only Ser447Ter and C49620T variants were associated with increased LDL-C in sub-Saharan Africa. Despite few studies available in this context in the literature, certain genetic variants were consistently associated with dyslipidemia especially in Northern Africa as highlighted in this analysis. Further data, particularly from genome-wide association studies, would help establish an African-specific reference for genetic susceptibility markers of dyslipidemia.
| S-EPMC7001384 | biostudies-literature
Project description:Background: Esophageal squamous cell carcinoma (ESCC), one of the most aggressive cancers, is endemic in Sub-Saharan Africa, constituting a major health burden. It has the most divergence in cancer incidence globally, with high prevalence reported in East Asia, Southern Europe, and in East and Southern Africa. Its etiology is multifactorial, with lifestyle, environmental, and genetic risk factors. Very little is known about the role of genetic factors in ESCC development and progression among African populations. The study aimed to systematically assess the evidence on genetic variants associated with ESCC in African populations. Methods: We carried out a comprehensive search of all African published studies up to April 2019, using PubMed, Embase, Scopus, and African Index Medicus databases. Quality assessment and data extraction were carried out by two investigators. The strength of the associations was measured by odds ratios and 95% confidence intervals. Results: Twenty-three genetic studies on ESCC in African populations were included in the systematic review. They were carried out on Black and admixed South African populations, as well as on Malawian, Sudanese, and Kenyan populations. Most studies were candidate gene studies and included DNA sequence variants in 58 different genes. Only one study carried out whole-exome sequencing of 59 ESCC patients. Sample sizes varied from 18 to 880 cases and 88 to 939 controls. Altogether, over 100 variants in 37 genes were part of 17 case-control genetic association studies to identify susceptibility loci for ESCC. In these studies, 25 variants in 20 genes were reported to have a statistically significant association. In addition, eight studies investigated changes in cancer tissues and identified somatic alterations in 17 genes and evidence of loss of heterozygosity, copy number variation, and microsatellite instability. Two genes were assessed for both genetic association and somatic mutation. Conclusions: Comprehensive large-scale studies on the genetic basis of ESCC are still lacking in Africa. Sample sizes in existing studies are too small to draw definitive conclusions about ESCC etiology. Only a small number of African populations have been analyzed, and replication and validation studies are missing. The genetic etiology of ESCC in Africa is, therefore, still poorly defined.
| S-EPMC6687768 | biostudies-literature
Project description:Warfarin is the most commonly used oral anticoagulant in sub-Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black-Africans, we performed a meta-analysis of 48 studies (2,336 patients). Significant predictors for CYP2C9 and stable dose included rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5), rs9332131 (CYP2C9*6), and rs28371685 (CYP2C9*11) reducing dose by 6.8, 12.5, 13.4, 8.1, and 5.3 mg/week, respectively. VKORC1 variants rs9923231 (-1639G>A), rs9934438 (1173C>T), rs2359612 (2255C>T), rs8050894 (1542G>C), and rs2884737 (497T>G) decreased dose by 18.1, 21.6, 17.3, 11.7, and 19.6 mg/week, respectively, whereas rs7294 (3730G>A) increased dose by 6.9 mg/week. Finally, rs12777823 (CYP2C gene cluster) was associated with a dose reduction of 12.7 mg/week. Few studies were conducted in Africa, and patient numbers were small, highlighting the need for further work in black-Africans to evaluate genetic factors determining warfarin response.
| S-EPMC7217737 | biostudies-literature
Project description:Hypertension (HTN) is a persistent public health problem affecting approximately 1.3 billion individuals globally. Treatment-resistant hypertension (TRH) is defined as high blood pressure (BP) in a hypertensive patient that remains above goal despite use of ≥3 antihypertensive agents of different classes including a diuretic. Despite a plethora of treatment options available, only 31.0% of individuals have their HTN controlled. Interindividual genetic variability to drug response might explain this disappointing outcome because of genetic polymorphisms. Additionally, the poor knowledge of pathophysiological mechanisms underlying hypertensive disease and the long-term interaction of antihypertensive drugs with blood pressure control mechanisms further aggravates the problem. Furthermore, in Africa, there is a paucity of pharmacogenomic data on the treatment of resistant hypertension. Therefore, identification of genetic signals having the potential to predict the response of a drug for a given individual in an African population has been the subject of intensive investigation. In this review, we aim to systematically extract and discuss African evidence on the genetic variation, and pharmacogenomics towards the treatment of HTN. Furthermore, in silico methods are utilized to elucidate biological processes that will aid in identifying novel drug targets for the treatment of resistant hypertension in an African population. To provide an expanded view of genetic variants associated with the development of HTN, this study was performed using publicly available databases such as PubMed, Scopus, Web of Science, African Journal Online, PharmGKB searching for relevant papers between 1984 and 2020. A total of 2784 articles were reviewed, and only 42 studies were included following the inclusion criteria. Twenty studies reported associations with HTN and genes such as AGT (rs699), ACE (rs1799752), NOS3 (rs1799983), MTHFR (rs1801133), AGTR1 (rs5186), while twenty-two studies did not show any association within the African population. Thereafter, an in silico predictive approach was utilized to identify several genes including CLCNKB, CYPB11B2, SH2B2, STK9, and TBX5 which may act as potential drug targets because they are involved in pathways known to influence blood pressure. Next, co-expressed genes were identified as they are controlled by the same transcriptional regulatory program and may potentially be more effective as multiple drug targets in the treatment regimens for HTN. Genes belonging to the co-expressed gene cluster, ACE, AGT, AGTR1, AGTR2, and NOS3 as well as CSK and ADRG1 showed enrichment of G-protein-coupled receptor activity, the classical targets of drug discovery, which mediate cellular signaling processes. The latter is of importance, as the targeting of co-regulatory gene clusters will allow for the development of more effective HTN drug targets that could decrease the prevalence of both controlled and TRH.
| S-EPMC8067483 | biostudies-literature
Project description:Background: Despite hypertension being highly prevalent in individuals with African-ancestry, they are under-represented in large genome-wide association studies. Inclusion of African participants is essential to better understand genetic associations with blood pressure-related traits in Africans. This systematic review critically evaluates existing studies with African-ancestry participants and identifies knowledge gaps. Methods: We followed the PRISMA protocol, HuGE Review handbook to identify literature on original research, in English, on genetic association studies for blood pressure-related traits (systolic and diastolic blood pressure, pulse and mean-arterial pressure, and hypertension) in populations with African-ancestry (January 2007 to April 2020). A narrative synthesis of the evidence was conducted. Results: Twelve studies with African-ancestry participants met the eligibility criteria, within which 10 studies met the additional genetic association data criteria (i.e., reporting only on African-ancestry participants). Across the five blood pressure-related traits, 26 genome-wide significantly associated SNPs were identified, with six SNPs linked to more than one trait, illustrating pleiotropic effects. Among the SNP associations, 12 had not previously been described in non-African studies. Discussion: The limited number of relevant studies highlights the dearth of genomic association studies on participants with African-ancestry, especially those located within Africa. Variations in study methodology, participant inclusion, adjustment for covariates (e.g., antihypertensive medication) and relatively small sample sizes make comparisons challenging, and have resulted in fewer significant associations, compared to large European studies. Regional variation in the prevalence and associated risk factors of hypertension across Africa makes a compelling argument to develop African cohorts to facilitate large genomic studies, using African-centric arrays. Data harmonisation and comparable study designs, such as described in the H3Africa CHAIR initiative, provide a good example toward achieving this goal. Other relevant information: SS and J-TB were funded by the South African National Research Foundation. MR is a South African Research Chair in Genomics and Bioinformatics of African populations hosted by the University of the Witwatersrand, funded by the Department of Science and Innovation, and administered by the NRF. This review was registered at PROSPERO (registration number: CRD42020179221) and OSF (registration DOI: 10.17605/OSF.IO/QT2HA).
| S-EPMC8564494 | biostudies-literature
Project description:Obesity-associated metabolic illnesses are increasing at an alarming rate in Asian countries. A common feature observed in the Asian population is a higher incidence of abdominal obesity-the "skinny-fat" Asian syndrome. In this review, we critically evaluate the relative roles of genetics and environmental factors on fat distribution in Asian populations. While there is an upward trend in obesity among most Asian countries, it appears particularly conspicuous in Malaysia. We propose a novel theory, the Malaysian gene-environment multiplier hypothesis, which explains how ancestral variations in feast-and-famine cycles contribute to inherited genetic predispositions that, when acted on by modern-day stressors-most notably, urbanization, westernization, lifestyle changes, dietary transitions, cultural pressures, and stress-contribute to increased visceral adiposity in Asian populations. At present, the major determinants contributing to visceral adiposity in Asians are far from conclusive, but we seek to highlight critical areas for further research.
| S-EPMC7803598 | biostudies-literature
Project description:BackgroundHigh blood pressure is an important public health concern and the leading risk factor for global mortality and morbidity. To assess the implications of this condition, we aimed to review the existing literature and study the factors that are significantly associated with hypertension in the Pakistani population.MethodsWe conducted several electronic searches in PubMed, ISI Web of Science, PsycINFO, EMBASE, Scopus, Elsevier, and manually searched the citations of published articles on hypertension from May 2019 to August 2019. We included all studies that examined factors associated with hypertension regardless of the study design. To assess the quality of the research, we used the Newcastle-Ottawa Quality Assessment Scale. We also conducted meta-analyses using the DerSimonian & Laird random-effects model to collate results from at least three studies.ResultsWe included 30 cross-sectional and 7 case-control studies (99,391 participants country-wide) in this review and found 13 (35.1%) to be high-quality studies. We identified 5 socio-demographic, 3 lifestyle, 3 health-related, and 4 psychological variables that were significantly associated with hypertension. Adults aged between 30-60 years who were married, living in urban areas with high incomes, used tobacco, had a family history of hypertension, and had comorbidities (overweight, obesity, diabetes, anxiety, stress, and anger management issues) were positively associated with hypertension. On the other hand, individuals having high education levels, normal physical activity, and unrestricted salt in their diet were negatively associated with hypertension.ConclusionWe found several socio-demographic, lifestyle, health-related, and psychological factors that were significantly (positively and negatively) associated with hypertension. Our findings may help physicians and public health workers to identify high-risk groups and recommend appropriate prevention strategies. Further research is warranted to investigate these factors rigorously and collate global evidence on the same.
| S-EPMC7845984 | biostudies-literature
Project description:Background: The metabolic syndrome (MetS) is prevalent in Arabian populations. Several small-scale studies have been performed to investigate the genetic basis of MetS. This systematic review and meta-analysis aimed to examine whether candidate gene polymorphisms are associated with MetS susceptibility among ethnic groups of the Arabian world and to suggest possible directions for future research regarding genetic markers and MetS. Methods: A search was conducted for peer-reviewed articles that examined the genetic association of MetS in Arabian populations in the following databases: Medline, Embase, Scopus, Direct Science, Web of Science, ProQuest, and Google Scholar until March 31, 2021. Articles were eligible if they were case-control studies, which investigated MetS as a dichotomous outcome (MetS vs no MetS). To assess the quality of the studies, the Q-Genie tool (Quality of Genetic Association Studies) was used. A non-central chi2 (random-effect) distribution was used to determine the heterogeneity (H) of Q and I (Galassi et al., The American journal of medicine, 2006, 119, 812-819) statistics. Results: Our search strategy identified 36 studies that met our inclusion criteria. In most cases, studies were excluded due to a lack of statistical information such as odds ratios, confidence intervals, and p-values. According to the Q-Genie tool, 12 studies scored poorly (a score of≤35), 13 studies scored moderately ( >35 and≤45), and 12 studies had good quality ( >45 or higher). The most frequently studied genes were FTO and VDR (both included in four studies). Three SNPs indicated increased risk for MetS after calculating the pooled odds ratios: FTO-rs9939609 (odds ratio 1.49, 95% CI: 0.96-2.32); LEP-rs7799039 (odds ratio 1.85, 95% CI: 1.37-2.5); and SERPINA12-rs2236242 (odds ratio 1.65, 95% CI: 1.21-2.24). Meta-analysis studies showed no significant heterogeneity. Conclusion: There were many sources of heterogeneity in the study settings. Most of the studies had low to moderate quality because of sample size and power issues, not considering all potential sources of bias, and not providing details about genotyping methods and results. As most studies were small-scale, aimed to replicate findings from other populations, we did not find any unique genetic association between MetS and Arabian populations.
| S-EPMC8637276 | biostudies-literature
Project description:BACKGROUND:Patients with chronic conditions and limited access to health care experience stressful challenges resulting from the burden of managing both their conditions and their daily life demands. Resilience provides a mechanism of adapting to stressful experiences. We conducted a systematic review and meta-analysis to synthesize the evidence about interventions to enhance resiliency in managing hypertension or type 2 diabetes in vulnerable populations and to assess the efficacy of these interventions on clinical outcomes. METHODS:We searched multiple databases from early inception through February 2015 including randomized controlled trials that enrolled patients with type 2 diabetes or hypertension. All interventions that targeted resilience in vulnerable populations were included. Data were synthesized to describe the characteristics and efficacy of resiliency interventions. We pooled the total effects by calculating standardized mean difference using the random-effects model. RESULTS:The final search yielded 17 studies. All studies were conducted in the United States and generally targeted minority participants. Resiliency interventions used diverse strategies; discussion groups or workshops were the most common approach. CONCLUSIONS:Interventions aimed at enhancing the resiliency of patients from vulnerable groups are diverse. Outcomes were not fully conclusive. There was some evidence that resiliency interventions had a positive effect on hemoglobin A1C levels but not blood pressure. The incorporation of resiliency-oriented interventions into the arsenal of preventing and managing chronic conditions appears to be an opportunity that remains to be better investigated and exploited, and there is need to pursue further understanding of the core components of any intervention that claims to enhance resilience.
| S-EPMC4556590 | biostudies-literature
Project description:ObjectiveEthnic minority populations (EMPs) are disproportionally affected by hypertension-mediated complications compared with European host populations (EHPs), which might be due to disparities in hypertension awareness, treatment and control. We conducted a systematic review and meta-analysis to compare awareness, treatment and control rates among EMPs with EHPs.MethodsMEDLINE, EMBASE and Web of Science were searched from inception to 29 January 2020. Critical appraisal was performed according to methods of Hoy et al. Pooled odds ratios with corresponding 95% confidence intervals were calculated for these rates, stratified by ethnic group, using either random or fixed effect meta-analysis based on I2-statistics. Study was registered in PROSPRO (CRD42020107897).ResultsA total of 3532 records were screened of which 16 were included in the analysis with data on 26 800 EMP and 57 000 EHP individuals. Compared with EHPs, African origin populations were more likely to be aware (odds ratio 1.26, 95% confidence interval 1.02-1.56) and treated (1.49, 1.18-1.88) for hypertension, but were less likely to have their blood pressure controlled (0.56, 0.40-0.78), whereas South Asian populations were more likely to be aware (1.15, 1.02-1.30), but had similar treatment and control rates. In Moroccan populations, hypertension awareness (0.79, 0.62-1.00) and treatment levels (0.77, 0.60-0.97) were lower compared with EHPs, while in Turkish populations awareness was lower (0.81, 0.65-1.00).ConclusionLevels of hypertension awareness, treatment and control differ between EMPs and EHPs. Effort should be made to improve these suboptimal rates in EMPs, aiming to reduce ethnic inequalities in hypertension-mediated complications.
| S-EPMC7810417 | biostudies-literature