Contributions
Abstract: PB2407
Type: Publication Only
Background
Sickle cell disease (SCD) is a monogenic disease associated with multisystem morbidity. Clinical severity of SCD is extremely variable, and reasons for this heterogeneity are not fully understood. Inter-individual variation in hemoglobin F (HbF) level is likely one of the main modifiers that contribute to the clinical heterogeneity observed in SCD patients as it inhibits HbS polymerization and reduces the mean corpuscular HbS concentration. Previous studies showed association of variants at 3 major genomic loci with HbF levels.
Aims
To investigate the prevalence of BCL11A (rs11886868), HSB1L-MYB (rs9382268) and XmnI γG-158 (C/T) genetic polymorphisms in a cohort of Egyptian SCD patients and to clarify the possible association between these polymorphisms and HbF level before and after hydroxyurea (HU) therapy.
Methods
One hundred Egyptian SCD patients (53 females) with a mean age of 13.68±8.91 years followed up at Pediatric Hematology and BMT Unit, Children Hospital, Cairo University were enrolled. Hundred age and sex matched unrelated healthy children were included as a control group. Genotyping of the studied single nucleotide polymorphisms (SNPs) was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Informed consents were obtained from the parents or legal guardians of patients before enrollment and the study was approved by the Research Ethics Committee of Faculty of Medicine, Cairo University.
Results
The distribution of the studied SNPs did not differ between SCD patients and controls except for the heteromutant genotypes of BCL11A which was significantly higher in SCD patients (p=0.13). For the HSB1L-MYB, BCL11A and Xmn1, baseline HbF level was higher in patients having the polymorphic genotypes than those with the wild genotypes, yet the difference between them did not reach a statistically significant level (p=0.47, 0.95 and 0.19 respectively). Fold change of HbF after HU therapy did not differ between patients harboring the wild or the variant genotypes for each SNP either alone or when more than one SNP co-existed (p=0.12, 0.91 and 1 for HSB1L-MYB, BCL11A and Xmn1 respectively).
Conclusion
HSB1L and BCL11A genetic polymorphisms had no positive impact on HbF level. Identification of regulators of HbF expression might be promising and mechanisms mediating this switching process could lead to better, less toxic, and more effective strategies for HbF induction
Session topic: 27. Sickle cell disease
Keyword(s): Polymorphism, sickle cell disease
Abstract: PB2407
Type: Publication Only
Background
Sickle cell disease (SCD) is a monogenic disease associated with multisystem morbidity. Clinical severity of SCD is extremely variable, and reasons for this heterogeneity are not fully understood. Inter-individual variation in hemoglobin F (HbF) level is likely one of the main modifiers that contribute to the clinical heterogeneity observed in SCD patients as it inhibits HbS polymerization and reduces the mean corpuscular HbS concentration. Previous studies showed association of variants at 3 major genomic loci with HbF levels.
Aims
To investigate the prevalence of BCL11A (rs11886868), HSB1L-MYB (rs9382268) and XmnI γG-158 (C/T) genetic polymorphisms in a cohort of Egyptian SCD patients and to clarify the possible association between these polymorphisms and HbF level before and after hydroxyurea (HU) therapy.
Methods
One hundred Egyptian SCD patients (53 females) with a mean age of 13.68±8.91 years followed up at Pediatric Hematology and BMT Unit, Children Hospital, Cairo University were enrolled. Hundred age and sex matched unrelated healthy children were included as a control group. Genotyping of the studied single nucleotide polymorphisms (SNPs) was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Informed consents were obtained from the parents or legal guardians of patients before enrollment and the study was approved by the Research Ethics Committee of Faculty of Medicine, Cairo University.
Results
The distribution of the studied SNPs did not differ between SCD patients and controls except for the heteromutant genotypes of BCL11A which was significantly higher in SCD patients (p=0.13). For the HSB1L-MYB, BCL11A and Xmn1, baseline HbF level was higher in patients having the polymorphic genotypes than those with the wild genotypes, yet the difference between them did not reach a statistically significant level (p=0.47, 0.95 and 0.19 respectively). Fold change of HbF after HU therapy did not differ between patients harboring the wild or the variant genotypes for each SNP either alone or when more than one SNP co-existed (p=0.12, 0.91 and 1 for HSB1L-MYB, BCL11A and Xmn1 respectively).
Conclusion
HSB1L and BCL11A genetic polymorphisms had no positive impact on HbF level. Identification of regulators of HbF expression might be promising and mechanisms mediating this switching process could lead to better, less toxic, and more effective strategies for HbF induction
Session topic: 27. Sickle cell disease
Keyword(s): Polymorphism, sickle cell disease