5593300 INVESTIGATIONS OF KIDNEY DYSFUNCTION-RELATED GENE VARIANTS IN SICKLE CELL DISEASE PATIENTS IN CAMEROON (SUB-SAHARAN AFRICA)
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PROVIDER: S-EPMC10112602 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
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Project description:BackgroundRenal dysfunctions are associated with increased morbidity and mortality in sickle cell disease (SCD). Early detection and subsequent management of SCD patients at risk for renal failure and dysfunctions are essential, however, predictors that can identify patients at risk of developing renal dysfunction are not fully understood.MethodsIn this study, we have investigated the association of 31 known kidney dysfunctions-related variants detected in African Americans from multi-ethnic genome wide studies (GWAS) meta-analysis, to kidney-dysfunctions in a group of 413 Cameroonian patients with SCD. Systems level bioinformatics analyses were performed, employing protein-protein interaction networks to further interrogate the putative associations.ResultsUp to 61% of these patients had micro-albuminuria, 2.4% proteinuria, 71% glomerular hyperfiltration, and 5.9% had renal failure. Six variants are significantly associated with the two quantifiable phenotypes of kidney dysfunction (eGFR and crude-albuminuria): A1CF-rs10994860 (P = 0.02020), SYPL2-rs12136063 (P = 0.04208), and APOL1 (G1)-rs73885319 (P = 0.04610) are associated with eGFR; and WNT7A-rs6795744 (P = 0.03730), TMEM60-rs6465825 (P = 0.02340), and APOL1 (G2)-rs71785313 (P = 0.03803) observed to be protective against micro-albuminuria. We identified a protein-protein interaction sub-network containing three of these gene variants: APOL1, SYPL2, and WNT7A, connected to the Nuclear factor NF-kappa-B p105 subunit (NFKB1), revealed to be essential and might indirectly influence extreme phenotypes. Interestingly, clinical variables, including body mass index (BMI), systolic blood pressure, vaso-occlusive crisis (VOC), and haemoglobin (Hb), explain better the kidney phenotypic variations in this SCD population.ConclusionThis study highlights a strong contribution of haematological indices (Hb level), anthropometric variables (BMI, blood pressure), and clinical events (i.e., vaso-occlusive crisis) to kidney dysfunctions in SCD, rather than known genetic factors. Only 6/31 characterised gene-variants are associated with kidney dysfunction phenotypes in SCD samples from Cameroon. The data reveal and emphasise the urgent need to extend GWAS studies in populations of African ancestries living in Africa, and particularly for kidney dysfunctions in SCD.
| S-EPMC8005585 | biostudies-literature
Project description: Not available
| S-EPMC9426797 | biostudies-literature
Project description:Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness on high BP and temporary increasing screening for hypertension worldwide. We here provide the results of the 2017 MMM (MMM17) edition in Cameroon. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017 nationwide. BP measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. The campaign was advertised through various media and screening stations were set-up in local markets, churches, and outpatient departments of health facilities. In all, 16 093 individuals were screened during MMM17, of whom 4595 (29.2%) had hypertension. A total of 2742 (19.8%) of individuals not receiving anti-hypertensive medication were found to be hypertensive. Of those on medication, 1048 (57.2%) had uncontrolled BP. After adjusting for age, sex, and use of BP lowing medications, systolic and diastolic BPs were significantly higher in people on anti-hypertensive treatment, with higher waist circumference. MMM17 was the largest BP screening campaign undertaken in Cameroon, and although treatment and control rates are higher than previously reported, they are still well below optimum levels. MMM has highlighted the need for routine population-based surveys and suggests that opportunistic screening can identify significant numbers with raised BP.
| S-EPMC6479431 | biostudies-literature
Project description:In Africa, at least 240,000 children are born each year with sickle cell disease. Historically, in the absence of newborn screening and appropriate treatment, most such children died undiagnosed in early childhood. However, with increasing awareness of the condition and economic and epidemiologic transition, increasing numbers are surviving. Greater investments in basic and applied research in the African context, and increased sensitization or African ministries of health regarding the importance of this condition, could make a substantial difference to the lives and livelihoods of millions of people living with sickle cell disease on the continent and their families.
| S-EPMC6858853 | biostudies-literature
Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient.
2014-02-20 | GSE52791 | GEO
Project description:BackgroundHydroxyurea is an effective treatment for sickle cell anemia, but few studies have been conducted in sub-Saharan Africa, where the burden is greatest. Coexisting conditions such as malnutrition and malaria may affect the feasibility, safety, and benefits of hydroxyurea in low-resource settings.MethodsWe enrolled children 1 to 10 years of age with sickle cell anemia in four sub-Saharan countries. Children received hydroxyurea at a dose of 15 to 20 mg per kilogram of body weight per day for 6 months, followed by dose escalation. The end points assessed feasibility (enrollment, retention, and adherence), safety (dose levels, toxic effects, and malaria), and benefits (laboratory variables, sickle cell-related events, transfusions, and survival).ResultsA total of 635 children were fully enrolled; 606 children completed screening and began receiving hydroxyurea at a mean (±SD) dose of 17.5±1.8 mg per kilogram per day. The retention rate was 94.2% at 3 years of treatment. Hydroxyurea therapy led to significant increases in both the hemoglobin and fetal hemoglobin levels. Dose-limiting toxic events regarding laboratory variables occurred in 5.1% of the participants, which was below the protocol-specified threshold for safety. During the treatment phase, 20.6 dose-limiting toxic effects per 100 patient-years occurred, as compared with 20.7 events per 100 patient-years before treatment. As compared with the pretreatment period, the rates of clinical adverse events decreased with hydroxyurea use, including rates of vaso-occlusive pain (98.3 vs. 44.6 events per 100 patient-years; incidence rate ratio, 0.45; 95% confidence interval [CI], 0.37 to 0.56), nonmalaria infection (142.5 vs. 90.0 events per 100 patient-years; incidence rate ratio, 0.62; 95% CI, 0.53 to 0.72), malaria (46.9 vs. 22.9 events per 100 patient-years; incidence rate ratio, 0.49; 95% CI, 0.37 to 0.66), transfusion (43.3 vs. 14.2 events per 100 patient-years; incidence rate ratio, 0.33; 95% CI, 0.23 to 0.47), and death (3.6 vs. 1.1 deaths per 100 patient-years; incidence rate ratio, 0.30; 95% CI, 0.10 to 0.88).ConclusionsHydroxyurea treatment was feasible and safe in children with sickle cell anemia living in sub-Saharan Africa. Hydroxyurea use reduced the incidence of vaso-occlusive events, infections, malaria, transfusions, and death, which supports the need for wider access to treatment. (Funded by the National Heart, Lung, and Blood Institute and others; REACH ClinicalTrials.gov number, NCT01966731 .).
| S-EPMC6454575 | biostudies-literature
Project description:Konzo, a disease characterized by sudden, irreversible spastic paraparesis, affecting up to 10% of the population in some regions of Sub-Saharan Africa during outbreaks and is strongly associated with dietary exposure to cyanogenic bitter cassava. The molecular mechanisms underlying the development of konzo, remain largely unknown. Here, through an analysis of 16 individuals with konzo and matched healthy controls from the same outbreak zones, we identified 117 differentially methylated loci involved in numerous biological processes that may identify cyanogenic- sensitive regions of the genome, providing the first study of epigenomic alterations associated with sub-lethal cyanide exposure and a clinical phenotype.
2022-12-31 | GSE180119 | GEO
Project description:Precision medicine uses genomic guidance to improve drug treatment safety and efficacy. Prior knowledge of genetic variant impact can enable such strategies, but current knowledge of African variants remains scarce. G6PD variants are linked to haemolytic adverse effects for a number of drugs commonly used in African populations. We have investigated a set of G6PD variants with structural bioinformatics techniques to further characterise variants with known effect, and gain insights into variants with unknown impact. We observed wide variations in patterns of root-mean-square deviation between wild-type and variant structures. Variants with known, highly deleterious impact show structural effects which may likely result in the destabilisation of the G6PD homodimer. The V68M and N126D variants (which are both common across African populations, and together form the A- haplotype) induce large conformational shifts in the catalytic NADP+ binding domain. We observed a greater impact for the haplotype than for each of the individual variants in these cases. A novel African variant (M207T) shows the potential to disrupt interactions within the protein core, urging further investigation. We explore how characterising the molecular impact of African G6PD variants can enable advanced strategies for precision medicine, as well as impact the use of novel therapeutics aiming to treat G6PD deficiency. This knowledge can assist in bridging current knowledge gaps, and aid to facilitate precision medicine applications in African populations.
| S-EPMC8933681 | biostudies-literature
Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile bacteria in lower airway samples from 60 subjects
2014-02-20 | E-GEOD-52791 | biostudies-arrayexpress
Project description:Measurement of incidence rates of childhood cancer in Africa is difficult. The study 'Cancer of Childhood in sub Saharan Africa' [Stefan C, Bray F, Ferlay J, Parkin DM and Liu B (2017) Cancer of Childhood in sub-Saharan Africaecancer11(755)] brings together results from 16 population-based registries which, as members of the African Cancer Registry Network (AFCRN), have been evaluated as achieving adequate coverage of their target population. The cancers are classified according to the third revision of the International Classification of Childhood Cancer (ICCC-3) and recorded rates in Africa are compared with those in childhood populations in the UK, France, and the USA. It is clear that, in many centres, lack of adequate diagnostic and treatment facilities, leads to under-diagnosis (and enumeration) of leukaemias and brain cancers. However, for several childhood cancers, incidence rates in Africa are higher than those in high income countries. This applies to infection-related cancers such as Kaposi sarcoma, Burkitt lymphoma, Hodgkin lymphoma and hepatocellular carcinoma, and also to two common embryonal cancers-retinoblastoma and nephroblastoma. These (and other) observations are unlikely to be artefact, and are of considerable interest when considering possible aetiological factors, including ethnic differences in risk (and hence genetic/familial antecedents). The data reported are the most extensive so far available on the incidence of cancer in sub Saharan Africa, and clearly indicate the need for more resources to be devoted to cancer registration, especially in the childhood age range, as part of an overall programme to improve the availability of diagnosis and treatment of this group of cancers, many of which have-potentially-an excellent prognosis.
| S-EPMC5533598 | biostudies-other