Associations Between Sdf-1 Alpha Polymorphisms And Malarial Outcomes In Children At Siaya County Referal Hospital, Western Kenya

ABSTRACT

In high Plasmodium transmission regions, malaria caused by Plasmodium falciparum is the leading cause of malaria-related morbidity and mortality among children under the age of 5 years. Severe malaria anaemia (SMA) is the most common cause of malaria burden in holoendemic P. falciparum transmission regions such. Although the mechanisms underlying development of SMA are poorly understood, direct and indirect lysis of erythrocytes, suppression of erythropoiesis, erythrophagocytosis, dyserythropoiesis and dysregulation in pro- and anti-inflammatory response characterize low haemoglobin levels in malaria. Children under the age of 5 years lack naturally-acquired malarial immunity thus innate immunity provides the children with the first line of defence against P. falciparum infections. The risk for progression of malaria infection is partly accounted for by host genetic variations in immune mediators. Stromal cell derived factor (SDF)-1α (CXCL12) is an important mediator of immune, inflammatory and haematopoietic responses. In human malaria, the plasma level of SDF-1α is elevated in children presenting with cerebral malaria and mild-to-moderate anaemia. Even though several studies indicate that SDF-1α genetic variation regulate outcomes of HIV-1 infection, hematopoiesis, and cancer, the role of genetic variability in SDF-1α in P. falciparum infections has not been explored. Genotyping for SDF-1α single nucleotide polymorphisms (SNP) in the promoter (C -1002T; rs2839686) and 3′ UTR (A+801G; rs1801157), DNA was extracted from buccal swabs using the BuccalAmp™ DNA extraction kit (Epicentre Biotechnologies). Genomic DNA was amplified using the Genomiphi DNA amplification kit (GE Healthcare, Life Sciences,Amersham), and then the SNPs were genotyped using a Taqman®5′ allelicdiscrimination Assay-By-Design method according to manufacturer’s instructions (Applied Biosystems). Outcomes of P.falciparum malaria (parasitaemia, high-density parasitaemia, SMA, reticulocyte production index, RPI) in children aged