Association of Integrin Alpha 2 C807T and L-Selectin P213S Alleles Polymorphism with Clinical Severity of Sickle Cell Disease among Sudanese Patients

Abstract

This was analytical, hospital-based, case-control study, conducted at Gaafar Ibn-Auf Paediatric Tertiary Hospital in Khartoum from June 2015 to June 2017. The present study aimed to study the association of integrin alpha 2 (ITGA2) C807T and L-selectin (SELL) P213S Alleles polymorphism with clinical severity of sickle cell disease (SCD) among Sudanese patients. Venous blood samples were collected from homozygous SCD patients (n=133) and from apparently healthy, age and sex matched, Sudanese individuals (n=112) as controls to compare them with cases. Sociodemographic and clinical data were collected by a questionnaire and from the reporting forms. A modified scoring system was used to assess severity. It includes number of transfusions, hospitalizations and lifetime cumulative incidence of specific complications of SCD as described by the SCD cooperative study group. Blood was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Complete blood counts were measured by automated hematology analyzer (Sysmex KX 21-N), and retics were counted by the manual method. Patients’ age ranged from 1 year up to 37 with median ages of 7 years, (n=76)57% were females and (n=57)43% were males and came from different areas in Sudan. The genotype and alleles frequencies of ITGA2 C807T and LSelectin SELL P213S were found to be significantly different between patients

and

controls (P=0.002 and 0.000, respectively). In ITGA2 relative risk analysis of alleles, frequency showed that patients with the T allele were 5.4 times more likely to suffer from the hemolytic crisis, vaso-occlusive and ischemic stroke rather than patients with the C allele. There was a significant association between these gene polymorphisms and high expression of L-selectin by leukocytes, or the development of complications in SCD (P= 0.000). Hematologic parameters (Hb, RBCs, WBCs and PCV) were found to be statistically significantly higher in controls than in patients (P values = 0.000, 0.000, 0.045, 0.034, respectively), while retics significantly lower in controls (P= 0.034) and also when compared with severity groups for SCD, all of them gave statistically significant results with P=0.000 for each. These results indicated that the (P213S) polymorphism of SELL gene and (C807T) polymorphism of ITGA2 are associated with more complications and crisis, with ITGA2 T allele that appears to deliberately increase susceptibility to ischemic stroke and vasoocclusive and hemolytic crisis in Sudanese patients with SCD. Hematologic markers and CBC are useful markers for assessment of erythropoietic bone marrow activity in SCD patients with different severities. These alleles can be a target for new therapeutic approaches of SCD.