Influence of single nucleotide polymorphisms in the BCL11A and HBS1L-MYB gene on the HbF levels and clinical severity of sickle cell anaemia patients

Upadhye, Dipti; Jain, Dipty; Trivedi, Yogesh L.; Nadkarni, Anita; Ghosh, Kanjaksha; Colah, Roshan

doi:10.1007/s00277-016-2675-1

Cited by 5 publications

(3 citation statements)

References 13 publications

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“…25,26 However, associations between the BCL11A variants and specific SCA-related complications, such as VOC frequency 11,27 and stroke, 11,25 have shown conflicting results. We did not observe a statistically significant reduction in ≥3 VOC/year or stroke history with inheritance of the BCL11A T variant in the University of Ibadan cohort.…”

Section: Discussionmentioning

confidence: 99%

Associations of α-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts

et al. 2017

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Alpha-thalassemia and the BCL11A rs1427407 T allele are commonly observed in sickle cell anemia (SCA) patients and are associated with reduced hemolysis and higher hemoglobin F levels, respectively. We investigated whether a high-risk genetic profile, defined as SCA patients who did not inherit either α-thalassemia or the BCL11A rs1427407 T allele, had stronger associations with clinical and laboratory variables than the individual genetic components in the University of Ibadan cohort (n=249). We then replicated our findings in SCA cohorts from the University of Illinois at Chicago (UIC)(n=260) and Walk-Treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy (Walk-PHaSST)(n=387). High-risk was associated with higher reticulocytes (15.0% vs. 7.8%, P=0.08) and stroke history (6% vs. 1%, P=0.02) than standard risk patients and these associations were more significant than the individual genetic components in the University of Ibadan cohort. These findings were replicated in high-risk patients from UIC and Walk-PHaSST for reticulocytes (UIC: 13.5% vs. 11.8%, P=0.03; Walk-PHaSST: 9.6% vs. 8.2%, P=0.0003) and stroke history (UIC: 32% vs. 22%, P=0.07; Walk-PHaSST: 14% vs. 7%, P=0.01). On combined analysis, high-risk had strong associations with increased markers of hemolysis (hemoglobin β= −0.29, 95%CI: −0.50 to −0.09; P=0.006; reticulocyte% β=2.29, 95%CI: 1.31 to 3.25; P=1x10−5) and stroke history (OR=2.0, 95%CI: 1.3 to 3.0; P=0.0002), but no association with frequent vaso-occlusive crises (≥3/year). A high-risk genetic profile is associated with increased hemolysis and stroke history in three independent cohorts. This profile may help identify patients to prioritize for hydroxyurea and for closer monitoring strategies for stroke.

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Section: Discussionmentioning

confidence: 99%

Associations of α-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts

et al. 2017

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“…Earlier study by Upadhye et.al. suggested that the influence of other genetic modifiers like certain SNPs in BCL11A and HBS1L-MYB genes that influence HbF levels were associated with a milder clinical presentation in patients with SCD from Nagpur in central India ( 19 ). However, we have not looked at these modifiers in our cohort of affected babies.…”

Section: Discussionmentioning

confidence: 99%

Newborn Screening for Sickle Cell Disease Among Tribal Populations in the States of Gujarat and Madhya Pradesh in India: Evaluation and Outcome Over 6 Years

Thaker

Colah

Patel³

et al. 2022

Front. Med.

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Sickle cell disease (SCD) poses considerable public health problems in India. This study was undertaken to understand the clinical course of SCD among children identified during newborn screening programmes in Gujarat and Madhya Pradesh where the frequency of the HbS gene is high. A total of 8,916 newborn babies 8,411 from Gujarat and 505 from Madhya Pradesh were screened over 6 years (2010–2016) using HPLC and the diagnosis was confirmed by molecular analysis in a subset. A total of 128 babies (122 Gujarat, 6 Madhya Pradesh) were identified with sickle cell disease, of whom 87 (69 HbSS, 18 HbS-β thalassemia) from Gujarat were followed for 0.5–6.6 years. Acute painful events, severe anemia and fever with infections were the major complications and 23 babies required hospitalization. Severe to moderate clinical presentation was found in 13.8% babies with SCD whereas, 86.2% babies had a milder presentation. Presence of ameliorating factors (α-thalassemia and Xmn 1 polymorphism) did not have a discernible effect on the clinical severity. Parents of babies with SCD were educated and counseled for home care. Distribution of mobile phones to 44 families having babies with SCD was beneficial as it allowed regular contact with patients and their families. Genetic counseling to the affected families has increased the awareness and acceptance for prenatal diagnosis and 18 couples opted for prenatal diagnosis in subsequent pregnancies. SCD is not always mild among tribal groups in India. Therefore, facilities for early diagnosis and prophylactic treatment in the tertiary care centers should be made available. The difficulties in regular follow up of the babies in remote rural areas have also been highlighted.

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“…HBS1L-MYB genes are expressed in the precursor cells of the erythroid. HBS1L encodes a protein with apparent GTP binding activity and is included in different cellular processes while MYB encodes a transcription factor for erythroid differentiation in hematopoiesis [10].…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms of HBS1L-MYB (rs4895441 and rs9376090) in Egyptian Patients with Hemoglobinopathy

Omar¹,

Abd-Elhalim²,

El-Edel³

et al. 2020

OJBD

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Objective: Study the HBS1L-MYB (rs4895441 and rs9376090) genetic polymorphisms in Egyptian patients with β-thalassemia major and sickle cell disease and its relation to Hb F and severity of the disease. Background: Hb F is a predominant modulator for the severity of β-thalassemia major & sickle cell disease. Genetic polymorphism in the intergenic region (HBS1L-MYB) between GTP-binding elongation factor HBS1L and myeloblastosis oncogene MYB on chromosome 6q is associated with high fetal hemoglobin levels. Subjects and Methods: 150 subjects were included in this study. For all studied groups: Complete blood picture and serum ferritin were evaluated. For patients, hemoglobin variants were separated by High-performance liquid chromatography. Genotyping of HBS1L-MYB (rs4895441 & rs9376090) was evaluated by real-time polymerase chain reaction technique using TaqMan probe. Results: AG, CT genotypes, and G, C alleles of HBS1L-MYB (rs4895441 & rs9376090) were significantly high in sickle cell patients [OR (3.400); 95% C.I (1.482-7.799)], (p = 0.003) & [OR (4.522); 95% C.I (1.854-11.029)], (p = 0.001) respectively. Also, a significant association was detected between polymorphisms and disease severity. However, in β-thalassemia major, no significant association was detected. Conclusion: In sickle cell disease patients, Genetic polymorphisms in HBS1L-MYB (rs9376090 & rs4895441) affect the level of Hb F which could improve the prognosis of these patients.

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Influence of single nucleotide polymorphisms in the BCL11A and HBS1L-MYB gene on the HbF levels and clinical severity of sickle cell anaemia patients

Cited by 5 publications

References 13 publications

Associations of α-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts

Associations of α-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts

Newborn Screening for Sickle Cell Disease Among Tribal Populations in the States of Gujarat and Madhya Pradesh in India: Evaluation and Outcome Over 6 Years

Genetic Polymorphisms of HBS1L-MYB (rs4895441 and rs9376090) in Egyptian Patients with Hemoglobinopathy

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