Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate ...characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% female, hypertensive, aged 18 and above were recruited into the study from two centers in Ibadan, Nigeria. Hypertension was identified using JNCVII definition and was further grouped into four subtypes: controlled hypertension (CH), isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). Results. Systolic-diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5%) and IDH (4.9% versus 4.7%) were more prevalent among females, ISH (10.1% versus 6.2%) was higher among males (P=0.048). Female subjects were more obese (P<0.0001) and SDH was prevalent among the obese group. Conclusion. Gender and obesity significantly influenced the distribution of the hypertension subtypes. Characterization of hypertension by subtypes in genetic association studies could lead to identification of previously unknown genetic variants involved in the etiology of hypertension. Large-scale studies among various ethnic groups may be needed to confirm these observations.
Chronic kidney disease (CKD) is increasingly common in hospitalized patients and is associated with increased risk for in-hospital morbidity and mortality. However, data regarding the prevalence of ...CKD in the African hospitalized patient population are limited. We therefore examined the prevalence and associated factors of impaired renal function and albuminuria among adult patients admitted to the internal medicine wards of a hospital in Northeast Ethiopia.
A cross-sectional study was conducted from January 1 to April 30, 2020 at the inpatient settings of Dessie referral hospital. Data on demographics and medical history were obtained, and serum creatinine and albuminuria were analyzed. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation. CKD was defined as impaired eGFR (<60 ml/min/1.73m2) and/or albuminuria. Univariate and multivariable analysis were conducted to determine factors associated with impaired eGFR and albuminuria.
A total of 369 patients were included in this study. The prevalence of impaired eGFR was 19.0% (95%CI: 15.2%-23.2%) and albuminuria was 30.9% (95%CI: 26.3%-35.7%). Overall, 33.9% (95%CI: 29.2%-38.9%) of the patients had some degree of CKD, but only 21.6% (95%CI: 15.1%-29.4%) were aware of their renal disease. In multivariable analysis, older age, a family history of kidney disease, diabetes, hypertension and HIV were independently associated with both impaired eGFR and albuminuria while male gender was independently associated with only albuminuria.
CKD is common in adult patients admitted to the internal medicine wards, but only few patients are aware of their condition. These findings highlight the need for feasible approaches to timely identify kidney disease and raise awareness on the importance of detection and early intervention in the inpatient settings.
Abstract
To identify factors that affect manifestations of sickle cell anemia we compared patients 11-30 years of age from University of Ibadan, Ibadan, Oyo, Nigeria (n = 214) and University of ...Illinois at Chicago, Chicago, IL, USA (n = 209). Paralleling findings in the general populations of the two countries, the Chicago patients were more often overweight or obese as defined by the Centers for Disease Control and Prevention (Atlanta, GA, USA) guidelines, and more often had elevated blood pressure (BP) as defined by the National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD, USA guidelines. The Ibadan patients did not receive the pneumococcal vaccine or hydroxyurea (HU) therapy as frequently as the Chicago patients. Consistent with lower rates of elevated BP and increased body mass index (BMI), stroke history was less frequent in the Ibadan patients 18 years old. Furthermore, in combined analyses, systolic and diastolic BP directly correlated with BMI, and elevated weight status independently associated with history of stroke. Our findings are consistent with the possibility that higher values for BMI and BP in Chicago sickle cell anemia patients may contribute to an increased risk of stroke and highlights the need for measures to reduce these risk factors. On the other hand, lower pneumococcal vaccination and HU therapy rates in Ibadan patients highlights the need for more improved vaccination coverage and for studies to define the role of HU therapy in Africa.
Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have ...been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.
Although rheumatoid arthritis has been shown to have moderately strong genetic component, both linked loci identified in linkage analyses and susceptibility variants from association studies are ...short of adequately accounting for a comprehensive catalogue of the molecular factors underlying this complex disease. The objective of this study was to use supplementary phenotype based on cumulative hazard of rheumatoid arthritis to identify linkage evidence for new and additional rheumatoid arthritis loci in a genome-wide linkage analysis of 342 affected sibling pair families from the United Kingdom.
Using proportional hazards model, we estimated cumulative hazard of rheumatoid arthritis and then used it as a quantitative trait in a non-parametric multipoint variance component linkage analysis with 353 microsatellite markers distributed across the 22 autosomal chromosomes.
We identified 3 new loci with genome-wide suggestive linkage evidence for rheumatoid arthritis on 9q21.13, 15p11.1 and 20q13.33. Our results also confirmed previously reported linkage evidence in the HLA-DRB1 region on chromosome 6 and on locus 1q32.1.
This study demonstrates the potential for information gain through the use of supplementary phenotypes in genetic study of complex diseases to identify new and additional potential linked loci that are not detected by linkage analysis of traditional phenotypes; and our results provide further evidence of the involvement of multiple loci in the genetic aetiology of rheumatoid arthritis.
Numerous genes for monogenic kidney diseases with classical patterns of inheritance, as well as genes for complex kidney diseases that manifest in combination with environmental factors, have been ...discovered. Genetic findings are increasingly used to inform clinical management of nephropathies, and have led to improved diagnostics, disease surveillance, choice of therapy, and family counseling. All of these steps rely on accurate interpretation of genetic data, which can be outpaced by current rates of data collection. In March of 2021, Kidney Diseases: Improving Global Outcomes (KDIGO) held a Controversies Conference on “Genetics in Chronic Kidney Disease (CKD)” to review the current state of understanding of monogenic and complex (polygenic) kidney diseases, processes for applying genetic findings in clinical medicine, and use of genomics for defining and stratifying CKD. Given the important contribution of genetic variants to CKD, practitioners with CKD patients are advised to “think genetic,” which specifically involves obtaining a family history, collecting detailed information on age of CKD onset, performing clinical examination for extrarenal symptoms, and considering genetic testing. To improve the use of genetics in nephrology, meeting participants advised developing an advanced training or subspecialty track for nephrologists, crafting guidelines for testing and treatment, and educating patients, students, and practitioners. Key areas of future research, including clinical interpretation of genome variation, electronic phenotyping, global representation, kidney-specific molecular data, polygenic scores, translational epidemiology, and open data resources, were also identified.
Keywords: kidney disease; sickle cell disease; APOL1; ELMO1; APOA1 Sickle cell disease (SCD) and apolipoprotein L1 (APOL1) G1/G2 variants increase chronic kidney disease (CKD) risk in African ...Americans by poorly understood mechanisms. We applied bioinformatics to identify new candidate genes associated with SCD-related CKD. An interaction network demonstrated APOA1 connecting haemoglobin subunit beta (HBB) and APOL1 with 36 other candidate genes. Gene expression revealed upregulation of engulfment and cell motility 1 (ELMO1) and downregulation of APOA1 in the kidney cortex of SCD versus non-SCD mice. Analysis of candidate genes identified ELMO1 rs10951509 to be associated with albuminuria and APOA1 rs11216132 with haemoglobinuria in patients with SCD. A bioinformatic approach highlights ELMO1 and APOA1 as potentially associated with SCD nephropathy. CAPTION(S): Table S1. Variants in genes implicated in kidney structure and function associated with kidney disease in African Americans. Table S2. Hypertension-related genetic variants associated with kidney disease in African Americans. Table S3. Oxidative stress pathway genetic variants associated with kidney disease in African Americans. Table S4. Additional genes and pathways involved with kidney disease in African Americans. Table S5. Gene enrichment pathway analysis for genes in an interaction network related to kidney disease in African Americans. The shaded Pathway includes ELMO1. Byline: Santosh L. Saraf, Xu Zhang, Binal N. Shah, Rasha Raslan, Bamidele O. Tayo, James P. Lash, Nora Franceschini, Victor R. Gordeuk
There are few studies of familial aggregation of blood pressure in African populations. This study was undertaken to provide estimates of heritability for four blood pressure phenotypes: systolic ...blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure.
A population-based sample of 528 pedigrees or extended families, comprising 1825 measured individuals, was studied in a poor urban community in Ibadan, Nigeria.
The mean SBP was 121.7 (SD 22.6) mmHg for men and 120.7 (SD 26.8) mmHg for women, while the mean DBP was 74.6 (SD 14.1) mmHg for men and 75.5 (SD 15.2) mm Hg for women. The study sample was lean mean body mass index (BMI) approximately 21 kg/m2. Maximum-likelihood heritability estimates were obtained under a polygenic model with simultaneous estimation of household effects using a variance components method, as implemented in the SOLAR software package. Heritability estimates of the traits were 34% for SBP, 29% for DBP, 36% for MAP and 13% for pulse pressure. Household effects were statistically significant for DBP (7.1%) and MAP (4.5%). Measured covariates (age, sex and BMI) accounted for 25, 24, 26 and 16% of the total variance, respectively, for SBP, DBP, MAP and pulse pressure.
These figures suggest that, similar to that reported in other populations, blood pressure is a heritable trait. Studies similar to this are needed to describe the familial aggregation of other complex traits in sub-Saharan African populations and to serve as a prelude to the identification of susceptibility genes involved in the pathophysiology of common complex diseases, including blood pressure and hypertension.
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