2022 |
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![]() | Palwende Romuald Boua, Jean-Tristan Brandenburg, Ananyo Choudhury, Hermann Sorgho, Engelbert A. Nonterah, Godfred Agongo, Gershim Asiki, Lisa Micklesfield, Solomon Choma, Francesc Xavier Gómez-Olivé, Scott Hazelhurst, Halidou Tinto, Nigel J. Crowther, Christopher G. Mathew, Michèle Ramsay Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans. (Journal Article) In: Nature communications, vol. 13, iss. 1, pp. 855, 2022. (Abstract | Links | BibTeX | Altmetric | Tags: Adult, Africa South of the Sahara, Atherosclerosis/*genetics/*pathology, Autoantigens/genetics, Cardiovascular Diseases/genetics, Carotid Intima-Media Thickness/*statistics & numerical data, Endocrine-Gland-Derived/genetics, Female, Gastrointestinal Hormones/genetics, Genetic Predisposition to Disease/*genetics, Genome/genetics, Histones/genetics, Humans, Male, Middle Aged, Polymorphism, Ribonucleoproteins/genetics, Sex Factors, Single Nucleotide/genetics, Sorting Nexins/genetics, Vascular Endothelial Growth Factor) @article{Boua2022, Atherosclerosis precedes the onset of clinical manifestations of cardiovascular diseases (CVDs). We used carotid intima-media thickness (cIMT) to investigate genetic susceptibility to atherosclerosis in 7894 unrelated adults (3963 women, 3931 men; 40 to 60 years) resident in four sub-Saharan African countries. cIMT was measured by ultrasound and genotyping was performed on the H3Africa SNP Array. Two new African-specific genome-wide significant loci for mean-max cIMT, SIRPA (p = 4.7E-08), and FBXL17 (p = 2.5E-08), were identified. Sex-stratified analysis revealed associations with one male-specific locus, SNX29 (p = 6.3E-09), and two female-specific loci, LARP6 (p = 2.4E-09) and PROK1 (p = 1.0E-08). We replicate previous cIMT associations with different lead SNPs in linkage disequilibrium with SNPs primarily identified in European populations. Our study find significant enrichment for genes involved in oestrogen response from female-specific signals. The genes identified show biological relevance to atherosclerosis and/or CVDs, sex-differences and transferability of signals from non-African studies. |
2021 |
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Journal Articles |
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![]() | Yeka Adoke, Rella Zoleko-Manego, Serge Ouoba, Alfred B Tiono, Grace Kaguthi, Juv^encio Eduardo Bonzela, Tran Thanh Duong, Alain Nahum, Marielle Bouyou-Akotet, Bernhards Ogutu, Alphonse Ouedraogo, Fiona Macintyre, Andreas Jessel, Bart Laurijssens, Mohammed H Cherkaoui-Rbati, Cathy Cantalloube, Anne Claire Marrast, Rapha"el Bejuit, David White, Timothy N C Wells, Florian Wartha, Didier Leroy, Afizi Kibuuka, Ghyslain Mombo-Ngoma, Daouda Ouattara, Ir`ene Mugenya, Bui Quang Phuc, Francis Bohissou, Denise P Mawili-Mboumba, Fredrick Olewe, Issiaka Soulama, Halidou Tinto, FALCI Study Group In: Malar. J., vol. 20, no. 1, pp. 222, 2021, ISSN: 1475-2875, (PMID: 34011358 PMCID: PMC8135182). (Abstract | Links | BibTeX | Altmetric | Tags: Adamantane/administration & dosage/analogs & derivatives, Adolescent, Adult, Aged, Aminoquinolines/administration & dosage, Benin, Burkina Faso, C580Y, Child, Combination treatment, Double-Blind Method, Drug Combinations, Exposure–response, Falciparum/prevention & control, Female, Ferroquine, Ferrous Compounds/administration & dosage, Gabon, Humans, Infant, Kelch-13 mutation, Kenya, Malaria, Male, Metallocenes/administration & dosage, Middle Aged, Mozambique, Parasite clearance, Peroxides/administration & dosage, Pharmacokinetics/pharmacodynamics, Plasmodium falciparum/drug effects, Preschool, resistance, Uganda, Vietnam, Vomiting, Young Adult) @article{Adoke2021-el, BACKGROUND: For uncomplicated Plasmodium falciparum malaria, highly efficacious single-dose treatments are expected to increase compliance and improve treatment outcomes, and thereby may slow the development of resistance. The efficacy and safety of a single-dose combination of artefenomel (800 mg) plus ferroquine (400/600/900/1200 mg doses) for the treatment of uncomplicated P. falciparum malaria were evaluated in Africa (focusing on children $łeq$ 5 years) and Asia. METHODS: The study was a randomized, double-blind, single-dose, multi-arm clinical trial in patients aged > 6 months to 5 years and 20 Asian patients. None of the treatment arms met the target efficacy criterion for PCR-adjusted ACPR at Day 28 (lower limit of 95% confidence interval [CI] > 90%). PCR-adjusted ACPR at Day 28 [95% CI] in the PP Set ranged from 78.4% [64.7; 88.7%] to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg ferroquine dose. Efficacy rates were low in Vietnamese patients, ranging from 20 to 40%. A clear relationship was found between drug exposure (artefenomel and ferroquine concentrations at Day 7) and efficacy (primary endpoint), with higher concentrations of both drugs resulting in higher efficacy. Six distinct kelch-13 mutations were detected in parasite isolates from 10/272 African patients (with 2 mutations known to be associated with artemisinin resistance) and 18/20 Asian patients (all C580Y mutation). Vomiting within 6 h of initial artefenomel administration was common (24.6%) and associated with lower drug exposures. CONCLUSION: The efficacy of artefenomel/ferroquine combination was suboptimal in African children aged $łeq$ 5 years, the population of interest, and vomiting most likely had a negative impact on efficacy. Trial registration ClinicalTrials.gov, NCT02497612. Registered 14 Jul 2015, https://clinicaltrials.gov/ct2/show/NCT02497612?term=NCT02497612&draw=2&rank=1. |
![]() | Engelbert A Nonterah, Michiel L Bots, Abraham Oduro, Godfred Agongo, Cassandra C Soo, Lisa K Micklesfield, Felistas Mashinya, Palwendé R Boua, Shukri F Mohamed, Alisha N Wade, Catherine Kyobutungi, Halidou Tinto, Shane A Norris, Stephen M Tollman, Mich`ele Ramsay, Diederick E Grobbee, Kerstin Klipstein-Grobusch, Nigel J Crowther, AWI-Gen, H3Africa Consortium Adiposity phenotypes and subclinical atherosclerosis in adults from sub-Saharan Africa: An H3Africa AWI-gen study (Journal Article) In: Glob. Heart, vol. 16, no. 1, pp. 19, 2021, ISSN: 2211-8179 2211-8160, (Copyright: © 2021 The Author(s). PMID: 33833943 PMCID: PMC7977036). (Abstract | Links | BibTeX | Altmetric | Tags: adiposity, Adult, Body Mass Index, cardiovascular disease, Carotid intima-media thickness, Cross-Sectional Studies, Female, Ghana, Humans, Male, Middle Aged, obesity, Obesity/complications/epidemiology, Phenotype, Risk Factors, sub-Saharan Africa, subclinical atherosclerosis) @article{Nonterah2021-pc, Background: Obesity and adipose tissue distribution contribute to an increased risk of cardiovascular disease (CVD) by promoting atherosclerosis. This association has been poorly studied in sub-Saharan Africa (SSA) despite the rising prevalence of cardiovascular disease. Objectives: We determined the association between various adiposity phenotypes and carotid intima-media thickness (CIMT), a proxy of subclinical atherosclerosis, in a large SSA population. Methods: A population-based cross-sectional study was performed from 2013-2016 in Burkina Faso, Ghana, Kenya and South Africa. Body mass index (BMI), waist (WC), hip circumferences (HC), visceral (VAT) and subcutaneous adipose tissue (SCAT) using B-mode ultrasound were measured. Ultrasonography of left and right far wall CIMT of the common carotid artery was used as an indicator of subclinical atherosclerosis. Individual participant data meta-analyses were used to determine the associations between adiposity phenotypes and CIMT in the pooled sample while adjusted multivariable linear regression analyses were used for site specific analyses. Results: Data were obtained from 9,010 adults (50.3% women and a mean age of 50$pm$ 6years). Men had higher levels of visceral fat than women while women had higher BMI, waist and hip circumference and subcutaneous fat than men at all sites except Burkina Faso. In the pooled analyses, BMI ($beta$-value [95% CIs]: 19.5 [16.8, 22.3] $mu$m) showed the strongest relationship with CIMT followed by VAT (5.86 [4.65, 7.07] $mu$m), SCAT (5.00 [2.85, 7.15] $mu$m), WC (1.27 [1.09, 1.44] $mu$m) and HC (1.23 [1.04, 1.42] $mu$m). Stronger associations were observed in men than in women. Conclusion: Obesity within SSA will likely result in higher levels of atherosclerosis and promote the occurrence of cardio- and cerebrovascular events, especially in males, unless addressed through primary prevention of obesity in both rural and urban communities across Africa. The inverse association of VAT with CIMT in Burkina Faso and Ghana requires further investigation. Highlights: All adiposity phenotypes were positively associated with common carotid intima-media thickness (CIMT) in the entire cohort (pooled analyses).BMI had the strongest association with CIMT compared to other phenotypes.The magnitude of association between adiposity phenotypes and CIMT was higher in men than in women.Subcutaneous adipose tissue was inversely associated with CIMT only in women.An unexpected finding was the inverse association of visceral adipose tissue with CIMT in Burkina Faso and Ghana. |
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