Pediatrics
Contributions
Type: Publication Only
Background
Sickle cell disease (SCD), well-known for its clinical and hematologic variability, comprises a heterogeneous group of hemoglobin genotypes where affected individuals have sickle hemoglobin (HbS). This considerable clinical heterogeneity among SCD patients is still not well understood. Genetic variants that modulate fetal hemoglobin (HbF) level have a strong impact on ameliorating the clinical phenotype.
Aims
The current study aimed to evaluate the prevalence of Xmn1 γG-158 (C/T) gene polymorphism in an Egyptian cohort of SCD patients and to investigate the possible association between this polymorphism and HbF level.
Methods
This case control study included 111 Egyptian SCD patients aged 1-21 years (mean age 11.08±5.5 years; 77 HbSS and 34 S/β thalassemia) and 100 age and gender matched unrelated healthy controls. All subjects were recruited only after informed consents were freely obtained from their guardians. Genotyping of Xmn1 γG-158 (C/T) polymorphism was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method.
Results
In our cohort, wild genotype Xmn1 (-/-) was the most prevalent (91.9%), while polymorphic genotypes whether heterozygous or homozygous (-/+ and +/+) were detected in 8.1% of SCD patients; six (6/77-7.8%) were HbSS and three (3/34-8.8%) were S/β thalassemia. No statistically significant differences were detected between SCD patients and controls or between HbSS and S/ β-thalassemia patients regarding prevalence of Xmn1 polymorphic genotypes (p=0.50 and 0.73 respectively). Baseline hemoglobin, HbF level and mean corpuscular volume were significantly higher in patients harboring polymorphic genotypes (p=0.01, 0.001 and 0.04 respectively). We found no significant effect of γG-158 (C/T) polymorphism on age of first transfusion, vasoocclusive crisis frequency or transfusion frequency (p=0.067, 0.778 and 0.053 respectively). Although HbF level was significantly higher in patients with polymorphic genotypes (19.24±7.0 vs. 9.06±7.45, p<0.001), Xmn1 γG-158 (C/T) polymorphism did not seem to influence HbF levels in patients receiving hydroxycarbamide (p=0.68, 95% Confidence interval= 5.08-7.68). By multiple regression analysis, only baseline HbF correlated independently with elevation of HbF in response to hydroxycarbamide therapy (p<0.001, 95% Confidence interval = 0.75-1.31).
Summary
Egyptian sickle patients have low frequency of Xmn1 γG-158 (C/T) polymorphism. The presence of Xmn1 γG-158 (C/T) polymorphism had positive influence on HbF level.
Keyword(s): Polymorphism, Sickle cell disease
Session topic: Publication Only
Type: Publication Only
Background
Sickle cell disease (SCD), well-known for its clinical and hematologic variability, comprises a heterogeneous group of hemoglobin genotypes where affected individuals have sickle hemoglobin (HbS). This considerable clinical heterogeneity among SCD patients is still not well understood. Genetic variants that modulate fetal hemoglobin (HbF) level have a strong impact on ameliorating the clinical phenotype.
Aims
The current study aimed to evaluate the prevalence of Xmn1 γG-158 (C/T) gene polymorphism in an Egyptian cohort of SCD patients and to investigate the possible association between this polymorphism and HbF level.
Methods
This case control study included 111 Egyptian SCD patients aged 1-21 years (mean age 11.08±5.5 years; 77 HbSS and 34 S/β thalassemia) and 100 age and gender matched unrelated healthy controls. All subjects were recruited only after informed consents were freely obtained from their guardians. Genotyping of Xmn1 γG-158 (C/T) polymorphism was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method.
Results
In our cohort, wild genotype Xmn1 (-/-) was the most prevalent (91.9%), while polymorphic genotypes whether heterozygous or homozygous (-/+ and +/+) were detected in 8.1% of SCD patients; six (6/77-7.8%) were HbSS and three (3/34-8.8%) were S/β thalassemia. No statistically significant differences were detected between SCD patients and controls or between HbSS and S/ β-thalassemia patients regarding prevalence of Xmn1 polymorphic genotypes (p=0.50 and 0.73 respectively). Baseline hemoglobin, HbF level and mean corpuscular volume were significantly higher in patients harboring polymorphic genotypes (p=0.01, 0.001 and 0.04 respectively). We found no significant effect of γG-158 (C/T) polymorphism on age of first transfusion, vasoocclusive crisis frequency or transfusion frequency (p=0.067, 0.778 and 0.053 respectively). Although HbF level was significantly higher in patients with polymorphic genotypes (19.24±7.0 vs. 9.06±7.45, p<0.001), Xmn1 γG-158 (C/T) polymorphism did not seem to influence HbF levels in patients receiving hydroxycarbamide (p=0.68, 95% Confidence interval= 5.08-7.68). By multiple regression analysis, only baseline HbF correlated independently with elevation of HbF in response to hydroxycarbamide therapy (p<0.001, 95% Confidence interval = 0.75-1.31).
Summary
Egyptian sickle patients have low frequency of Xmn1 γG-158 (C/T) polymorphism. The presence of Xmn1 γG-158 (C/T) polymorphism had positive influence on HbF level.
Keyword(s): Polymorphism, Sickle cell disease
Session topic: Publication Only