IL-Iβ +3954 C / T Polymorphism and Its Clinical Associations in Egyptian Sickle Cell Disease Patients

  • Rasha Abdel-Raouf Abdel-Aziz Afifi Department of Pediatrics, Cairo University, Cairo, Egypt
  • Yasser Mohamad Sedky Department of Pediatrics, Cairo University, Cairo, Egypt
  • Hesham Abd Elkarim Faculty of Medicine, Cairo University, Cairo, Egypt
  • Shahira Kamal Anis Botros Department of Clinical Pathology, Cairo University, Cairo, Egypt
Keywords: Sickle cell disease; Interleukin-1 beta; Single nucleotide polymorphism; Hypertension; Pulmonary


Background: Sickle cell disease (SCD) is a hereditary disorder characterized by hemolytic anemia with different clinical manifestations. Patients with SCD exhibit a chronic inflammatory state and reduced length and quality of life. Interleukin-1 β (IL-1β) is important in acute and chronic diseases; and its single nucleotide polymorphisms (SNP) have been considered as predictors of prognosis in several inflammatory conditions. This study aimed at exploring IL-1β (+3954C/T) SNP as a potential genetic modifier and/or predictor of SCD clinical and laboratory phenotypes.

Materials and Methods: This cross-sectional study involved 50 SCD patients and 50 age, sex and ethnicity-matched healthy individuals. IL-1β (+3954C/T) SNP was identified by PCR-RFLP. Associations between IL-1β (+3954 C/T) SNP and the clinical and laboratory profiles of patients with SCD were studied.

Results: It was found that the homozygous mutant genotype TT was significantly higher in cases compared to controls [13(26%) vs. 3(6%) respectively; p=0.006, OR (95%CI): 5.505(1.460-20.756)]. The homozygous mutant genotype TT was associated with a higher mean pulmonary arterial pressure when compared to the CC and CT genotype (42.62 vs. 33.49 mmHg, p<0.001).

Conclusion: There is an increased prevalence of the mutant genotype of IL-1β +3954 SNP in Egyptian SCD patients. Regarding disease complications, the mutant genotype was more prevalent in cases complicated by pulmonary hypertension. These findings point to the possible role of IL-1β +3954 SNP in the pathophysiology of SCD and its manifestations.


Sonati MD & Costa FF. The genetics of blood disorders: hereditary hemoglobinopathies. J Pediatr (Rio J), 2008; 84 (4): S40–S51.

Conran N, Franco-Penteado CF and Costa FF. Newer aspects of the pathophysiology of sickle cell disease vaso-occlusion. Hemoglobin, 2009; 33: 1–16.

Aygun B & Odame I. A global perspective on sickle cell disease. Pediatric Blood & Cancer, 2012; 59 (2): 386–390.

Agasa B, Bosunga K, Opara A, Tshilumba K, Dupont E, Vertongen F, et al. Prevalence of sickle cell disease in a northeastern region of the Democratic Republic of Congo: What impact on transfusion policy? Transfusion Medicine, 2010; 20 (1): 62–65.

El-Beshlawy A & Youssry I. Prevention of hemoglobinopathies in Egypt. Hemoglobin; 2009; 33 (1): 14–20.

Abbasy A.S. Sickle cell anemia; first case reported from Egypt. Blood 1951; 6: 555-558.

Pathare A., Al Kindi S., Alnaqdy A.A., Daar S., Knox- Macaulay H. and Dennison D. Cytokine profile of sickle cell disease in Oman. American Journal of Hematology, 2004; 77, 323-328.

Steinberg MH. Predicting clinical severity in sickle cell anaemia. Br. J. Haematol. 2005; 129 (4): 465–481.

Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996; 87(6): 2095–2147.

Chen CJ, Shi Y, Hearn A, Fitzgerald K, Golenbock D, Reed G, et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J. Clin. Invest. 2006; 116: 2262–2271.

Pathare A, Kindi SA, Daar S, Dennison D. Cytokines in sickle cell disease, Hematology 2003; 8 (5): 329–337.

Brttain JE, Parise LV. Cytokines and plasma factors in sickle cell disease. Curr. Opin. Hematol. 2007;14 (5) : 438–443.

Pitanga TN, Vilas-Boas W, Cerqueira BAV, Seixas M O, Barbosa CG, Adorno EV, et al. Cytokine profiles in sickle cell anemia: Pathways to be unraveled. Advances in Bioscience and Biotechnology, 2013; 4: 6-12.

Vicari P, Adegoke SA, Mazzotti DR, Cançado RD, Nogutti MA, Figueiredo MS. Interleukin-1beta and interleukin- 6 gene polymorphisms are associated with manifestations of sickle cell anemia. Blood Cells Mol Dis, 2015; 54(3): 244–249.

Elliott L, Ashley-Koch AE, De Castro L, Jonassaint J, Price J, Ataga KI, et al. Genetic polymorphisms associated with priapism in sickle cell disease. Br. J. Haematol. 2007; 137 (3): 262–267.

Tarer V, Etienne-Julan M, Diara JP, Belloy MS, Mukizi-Mukaza M, Elion J, Romana M. Sickle Cell Disease in Guadeloupean children: pattern and prevalence of acute clinical events. Eur J Haematol. 2006; 76:193-199.

Gladwin T, Sachdev V, Jison L, Shizukuda Y, Plehn JF, Minter K, et al. Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Disease. N Engl J Med 2004; 350: 886-95.

Yock PG & Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 1984; 70(4): 657-662.

Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. Global burden of Sickle Cell Disease in children under five, modelling based on demographics, excess mortality, and interventions. PLoS Med. 2013; 10(7): e1001484.5.

Kornman KS. Interleukin 1 Genetics, Inflammatory Mechanisms, Nutrigenic Opportunities to Modulate Diseases of Aging. Am J Clin Nutr, 2006; 83: 475S -483S.

Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases, Blood 2011 ; 117 (14) : 3720–3732.

How to Cite
Afifi R, Sedky Y, Elkarim H, Botros S. IL-Iβ +3954 C / T Polymorphism and Its Clinical Associations in Egyptian Sickle Cell Disease Patients. Int J Hematol Oncol Stem Cell Res. 13(1):35-41.
Original Article(s)