Browsing by Subject "Sickle cell disease"
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- ItemOpen AccessThe co-inheritance of alpha-thalassemia and sickle cell anemia is associated with better hematological indices and lower consultations rate in Cameroonian patients and could improve their survival(Public Library of Science, 2014) Rumaney, Maryam Bibi; Bitoungui, Valentina Josiane Ngo; Vorster, Anna Alvera; Ramesar, Raj; Kengne, Andre Pascal; Ngogang, Jeanne; Wonkam, AmbroiseBACKGROUND: Co-inheritance of α-thalassemia was reported to be associated with a delayed age of disease onset among Cameroonian Sickle Cell Anemia (SCA) patients. The present study aimed to explore the correlation between α-thalassemia, hematological indices, and clinical events in these patients. Methods and FINDINGS: We studied 161 Cameroonian SCA patients and 103 controls (59.1% HbAA) with median ages of 17.5 and 23 years. RFLP-PCR was used to confirm SCA genotype and to describe haplotypes in the HBB-like genes cluster. Multiplex Gap-PCR was performed to investigate the 3.7 kb α-globin gene deletions. SNaPshot PCR, capillary electrophoresis and cycle sequencing were used for the genotyping of 10 SNPs in BCL11A , HMIP1/2 , OR51B5/6 and HBG loci, known to influence HbF levels. Generalised linear regression models adjusted for age, sex and SNPs genotypes was used to investigate effects of α-thalassemia on clinical and hematological indices. The median rate of vaso-occlusive painful crisis and hospitalisations was two and one per year, respectively. Stroke was reported in eight cases (7.4%). Benin haplotype was the most prevalent (66.3%; n = 208 chromosomes). Among patients, 37.3% ( n = 60) had at least one 3.7 kb deletion, compared to 10.9% ( n = 6) among HbAA controls (p<0.001). Among patients, the median RBC count increased with the number of 3.7 kb deletions [2.6, 3.0 and 3.4 million/dl, with no, one and two deletions (p = 0.01)]. The median MCV decreased with the number of 3.7 kb deletion [86, 80, and 68fl, with no, one and two deletions (p<0.0001)], as well as median WBC counts [13.2, 10.5 and 9.8×10 9 /L (p<0.0001. The co-inheritance of α-thalassemia was associated with lower consultations rate (p = 0.038). CONCLUSION: The co-inheritance of α-thalassemia and SCA is associated with improved hematological indices, and lower consultations rate in this group of patients. This could possibly improve their survival and explain the higher proportion of α-thalassemia among patients than controls.
- ItemOpen AccessIdentifying genetic variants and pathways associated with extreme levels of fetal hemoglobin in sickle cell disease in Tanzania(2020-06-05) Nkya, Siana; Mwita, Liberata; Mgaya, Josephine; Kumburu, Happiness; van Zwetselaar, Marco; Menzel, Stephan; Mazandu, Gaston K; Sangeda, Raphael; Chimusa, Emile; Makani, JulieBackground Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common genetic variants which differ across populations and hence do not fully account for HbF variation. Methods We investigated rare and common genetic variants that influence HbF levels in 14 SCD patients to elucidate variants and pathways in SCD patients with extreme HbF levels (≥7.7% for high HbF) and (≤2.5% for low HbF) in Tanzania. We performed targeted next generation sequencing (Illumina_Miseq) covering exonic and other significant fetal hemoglobin-associated loci, including BCL11A, MYB, HOXA9, HBB, HBG1, HBG2, CHD4, KLF1, MBD3, ZBTB7A and PGLYRP1. Results Results revealed a range of genetic variants, including bi-allelic and multi-allelic SNPs, frameshift insertions and deletions, some of which have functional importance. Notably, there were significantly more deletions in individuals with high HbF levels (11% vs 0.9%). We identified frameshift deletions in individuals with high HbF levels and frameshift insertions in individuals with low HbF. CHD4 and MBD3 genes, interacting in the same sub-network, were identified to have a significant number of pathogenic or non-synonymous mutations in individuals with low HbF levels, suggesting an important role of epigenetic pathways in the regulation of HbF synthesis. Conclusions This study provides new insights in selecting essential variants and identifying potential biological pathways associated with extreme HbF levels in SCD interrogating multiple genomic variants associated with HbF in SCD.
- ItemOpen AccessImplementation science research for the scale-up of evidence-based interventions for sickle cell disease in africa: a commentary(2021-02-17) Gyamfi, Joyce; Ojo, Temitope; Iwelunmor, Juliet; Ogedegbe, Gbenga; Ryan, Nessa; Diawara, Amy; Nnodu, Obiageli; Wonkam, Ambroise; Royal, Charmaine; Peprah, EmmanuelBackground The burden of sickle cell disease (SCD) is greatest among African nations. Effective scalability of evidence-based interventions (e.g., newborn screening, health education, prophylaxis for infection, optimal nutrition and hydration, hydroxyurea therapy, blood transfusions, and transcranial Doppler (TCD) screening) is urgently needed particularly in these settings for disease management. However, Africa is constrained by limited resources and the lack of capacity to conduct implementation science research for proper understanding of context, and assessment of barriers and facilitators to the uptake and scalability of evidence-based interventions (EBI) for SCD management. Main Body We outline implementation science approaches to embed EBI for SCD within the African context and highlight key implementation research programs for SCD management. Building implementation research capacity will meet the major need of developing effective life-long and accessible locally-tailored interventions for patients with SCD in Africa. Conclusion This commentary communicates the importance of the application of implementation science methodology to scale-up evidence-based interventions for the management of SCD in order to reduce pain, prevent other morbidities and premature death experienced by people with SCD in Africa, and improve their overall quality of life.
- ItemOpen AccessSAR1a promoter polymorphisms are not associated with fetal hemoglobin in patients with sickle cell disease from Cameroon(BioMed Central, 2017-05-12) Pule, Gift Dineo; Ngo Bitoungui, Valentina Josiane; Chemegni, Bernard Chetcha; Kengne, Andre Pascal; Wonkam, AmbroiseBackground: Reactivation of adult hemoglobin (HbF) is currently a dominant therapeutic approach to sickle cell disease (SCD). In this study, we have investigated among SCD patients from Cameroon, the association of HbF level and variants in the HU-inducible small guanosine triphosphate-binding protein, secretion-associated and RAS-related (SAR1a) protein, previously shown to be associated with HbF after HU treatment in African American SCD patients. Results: Only patients >5 years old were included; hemoglobin electrophoresis and a full blood count were conducted upon arrival at the hospital. RFLP-PCR was used to describe the HBB gene haplotypes and Gap PCR to investigate the 3.7 kb α-globin gene deletion. The iPLEX Gold Sequenom Mass Genotyping Array and cycle sequencing were used for the genotyping of four selected SNPs in SAR1a (rs2310991; rs4282891; rs76901216 and rs76901220). Genetic analysis was performed using an additive genetic model, under a generalized linear regression framework. 484 patients were studied. No associations were observed between any of the promoter variants and baseline HbF, clinical events or other hematological indices. Conclusion: The results of this study could be explained by possible population-specifcity of some tagging genomic variants associated with HbF production and illustrated the complexity of replicating HbF-promoting variants association results across African populations.
- ItemOpen AccessSickle cell disease, sickle trait and the risk for venous thromboembolism: a systematic review and meta-analysis(BioMed Central, 2018-10-04) Noubiap, Jean J; Temgoua, Mazou N; Tankeu, Ronni; Tochie, Joel Noutakdie; Wonkam, Ambroise; Bigna, Jean JoëlBackground Globally, sickle cell disease (SCD) is one of the most common haemoglobinopathy. Considered a public health problem, it leads to vessel occlusion, blood stasis and chronic activation of the coagulation system responsible for vaso-occlussive crises and venous thromboembolism (VTE) which may be fatal. Although contemporary observational studies suggest a relationship between SCD or sickle trait (SCT) and VTE, there is lack of a summary or meta-analysis data on this possible correlation. Hence, we propose to summarize the available evidence on the association between SCD, SCT and VTE including deep vein thrombosis (DVT) and pulmonary embolism (PE). Methods We searched PubMed and Scopus to identify all cross-sectional, cohort and case-control studies reporting on the association between SCD or SCT and VTE, DVT or PE in adults or children from inception to April 25, 2017. For measuring association between SCD or SCT and VTE, DVT, or PE, a meta-analysis using the random-effects method was performed to pool weighted odds ratios (OR) of risk estimates. Results From 313 records initially identified from bibliographic databases, 10 studies were eligible and therefore included the meta-analysis. SCD patients had significantly higher risk for VTE (pooled OR 4.4, 95%CI 2.6–7.5, p < 0.001), DVT (OR 1.1, 95% CI 1.1–1.2, p < 0.001) and PE (pooled OR 3.7, 95% CI 3.6–3.8, p < 0.001) as compared to non SCD-adults. A higher risk of VTE (OR 33.2, 95% CI 9.7–113.4, p < 0.001) and DVT (OR 30.7, 95% CI 1.6–578.2, p = 0.02) was found in pregnant or postpartum women with SCD as compared to their counterparts without SCD. Compared to adults with SCT, the risk of VTE was higher in adults with SCD (pooled OR 3.1, 95% CI 1.8–5.3, p < 0.001), and specifically in SCD pregnant or postpartum women (OR 20.3, 95% CI 4.1–102, p = 0.0003). The risk of PE was also higher in adults with SCD (OR 3.1, 95% CCI 1.7–5.9, p = 0.0004) as compared to those with SCT. The risk of VTE was higher in individuals with SCT compared to controls (pooled OR 1.7, 95% CI 1.3–2.2, p < 0.0001), but not in pregnant or postpartum women (OR 0.9, 95% CI 0.3–2.9, p = 0.863). Compared to controls, SCT was associated with a higher risk of PE (pooled OR 2.1, 95% CI 1.2–3.8, p = 0.012) but not of DVT (pooled OR 1.2, 95% CI 0.9–1.7, p = 0.157). Conclusion Individuals with SCD, especially pregnant or postpartum women, might have a higher risk of VTE compared to the general population. SCT might also increases the risk of VTE. However, currently available data are not sufficient to allow a definite conclusion. Further larger studies are needed to provide a definitive conclusion on the association between SCD, SCT and VTE.