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.
