ISSN 10227954, Russian Journal of Genetics, 2012, Vol. 48, No. 7, pp. 755–757. © Pleiades Publishing, Inc., 2012.
Sickle cell disease (SCD) is an inherited autosomal
recessive disorder. It is the first human monogenic dis
order characterized at the molecular level  in which
substitution of polar valine instead of nonpolar
glutamic acid at the sixth amino acid of the
chain causes production a defective hemoglobin,
known as sickle hemoglobin (HbS) [2, 3]. Although all
patients with SCD have the same mutation, severity of
their clinical manifestations are very different from
one to another . Some genetic modifiers are identi
fied for SCD including alpha thalassemia [5–7], ele
vated HbF, and glucose6phosphate dehydrogenase
(G6PD) deficiency. However these factors don’t com
pletely clarify the diversity in the clinical findings of
patients with SCD [6, 7]. Today, the introduction of
genome analysis due to the development in molecular
biology has been helpful to identify the genomic poly
morphisms responsible for the clinical diversity in
SCD. There are some evidences reporting the associa
tion between the single nucleotide polymorphisms
(SNPs) and stroke, leg ulceration, pulmonary hyper
tension, priapism and osteonecrosis, or different
responses to hydroxyurea . BSgene is correlated
with chromosomal haplotypes due to the pattern of
polymorphic sites that distributed at beta globin gene.
Haplotypes are named by it’s geographic distributions
. It can be distinguished by indirect method of
restriction fragment length polymorphism (RFLP). At
least 18 RFLPs have been reported across the
gene cluster that are adjacency linked. An occurrence of
0.068% meiose’s recombination within
cluster make linkage disequilibrium between polymor
phic sites (1 recombinant in 735 meioies) .
Some polymorphic sites were distributed across the
beta globin gene based on the results of the study in
The article is published in the original.
Saudi Arabia, two major forms of SCD have been rec
ognized including a benign and a severe form of the dis
ease . Some DNA polymorphisms in the
gene are associated with mild form of SCD .
Identification of polymorphisms associated with
benign form of SCD not only helps hematologist to
estimate the prognosis of the disease, but also can
present unnecessary therapeutic abortions by prenatal
In this cross sectional study, participants consist of
all patients with homozygous SCD who have been
referred to pediatric hematology clinic of Shiraz Uni
versity of Medical Sciences during the 6months
period from January 2010 to June 2010. Benign and
severe form of the disease were described based on
blood transfusion dependency. Patients were divided
into two groups including group 1: patients with no or
are transfusion (1–2 transfusion per year), and group 2:
patients who were transfusion dependent (every 1–2
Blood sampling (10cc EDTA) was done for each
patient. Analysis of Complete blood count was done by
a counter Model LUTON BEDS (Sysmex, England).
Column chromatography and cellulose acetate hemo
globin electrophoresis were performed to detect various
type of Hb and abnormal level of HbS .
Genomic DNA was extracted with a simple salting
out method .
Four polymorphic sites of
globin gene including:
were investigated in this
study. All samples were amplified by a PCR based
Instead of digestion enzyme we used specific prim
ers with a mismatched at the 3' end of the primer.
Linkage analysis was performed at polymorphic
restriction sites that were 5' to
by Hinf, 5' to
Polymorphisms Associated with Sickle Cell Disease in Southern Iran
S. Haghpanah, Sh. Nasirabadi, M. Kianmehr, A. Afrasiabi, and M. Karimi
Hematology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran
Received August 29, 2011
—Sickle cell disease (SCD) is an inherited autosomal recessive disorder. We aimed to describe the
spectrum of haplotypes of BSgene and to investigate a relationship with disease phenotype in patients with
SCD in Southern Iran. We didn’t find any significant association between BSglobin gene haplotypes and
clinical severity of the disease in an Iranian population. The exact mechanism by which the BSglobin gene
polymorphism affects clinical presentation is not obvious; however, further detailed studies at the molecular
level, with a larger sample size are required to show the mechanisms that influence the clinical presentation
of SCD in Iranian population.