Abstract:
Background Recent studies indicate that interferon gamma inducible chemokine, CXCL10, is a strong predictor of both human
and experimental cerebral malaria. We hypothesised malaria infection is associated with variation in CXCL10 expression. We determined whether polymorphisms in the CXCL10 gene promoter
region played a role in the clinical status of malaria patients and
addressed the genetic basis of CXCL10 expression during malaria
infection.
Methods Basic demographics that may impact our assessments
including age, gender, full blood count, sickle cell status and
CXCL10 polymorphism were assessed. We assessed a single
nucleotide polymorphism in the CXCL10 promoter (
–1447A>G
[rs4508917]) among 382 malaria and 117 non-malaria subjects
using PCR-restriction fragment length polymorphism assay.
Adjusted Odds Ratio (AOR) was used to
find out if there was any
association between CXC10 promoter polymorphism
–1447
A>G and susceptibility to malaria.
Results The median age for malaria patients was 4 years and that
for non-malaria was14 years. There was signi
ficant difference with
regards to haemoglobin levels and White cell counts between
malaria patients and non-malaria subjects ( p<0.0001).
Individuals with the 21447(A/G) genotype were susceptible to
malaria (adjusted odds ratio [AOR]=2.60, 95% CI: 1.51
–5.85,
p=0.021). Additionally, individuals with the 21447(A/G) genotype had significantly higher plasma CXCL10 levels than individuals with the 21447(A/A) genotype. Stratifying patients
according to gender, the observed association of malaria with over
expression of CXCL10 were more pronounced in females than in
male patients (AOR=5.47, 95% CI: 1.34
–22.29, p=0.018).
Conclusions Polymorphisms in the CXCL10 gene promoter
sequence were associated with increased CXCL10 production,
which is linked to severity of malaria. These results suggest that
the 21447A>G polymorphism in CXCL10 gene promoter could
be partly responsible for the reported variation underlying severity
of malaria outcomes particularly in females.
