Association between Cd14 (Cd14c-159t) Promoter Polymorphism and Susceptibility to Severe Malaria Anemia in Children, below 3 Years Resident in Siaya District, Western Kenya

Abstract

Among the infectious diseases worldwide, malaria is one of the leading causes of child morbidity and mortality. Severe malaria anemia (SMA) is the most common clinical manifestation of acute Plasmodium falciparum malaria in western Kenya, a holoendemic transmission area. It affects children aged between 3 and 36 months mostly, leading to morbidity and mortality in this region. Previous studies have associated variations in the promoter region of CD14, a gene which expresses as membrane-bound receptor (mCD14) and as soluble receptor (sCD14), with outcome of severe malaria in adult populations in some malaria endemic regions. However, the association between the CD14 C-159T and susceptibility to SMA in children resident in western Kenya is unknown. In addition, the distribution of allele frequencies in SMA and non-SMA children populations is unclear. As such, this cross-sectional study investigated the associations between polymorphisms in the CD14 C-159T andsusceptibility to SMA in children (n=240; aged 3-36 months),resident in P.falciparum holoendemic region of Siaya District, western Kenya. The allele frequencies in SMA versus non-SMA were also determined. The sample was drawn from a target population of 720children who present to the hospital with varying disease conditions in a year. The CD14 C-159T genotyping was carried out using a high-throughput TaqMan® single nucleotide polymorphism (SNP) genotyping assay technique. The association between CD14 C-159T genotypes and SMA was determined by multivariate logistic regression, controllingfor the confounding effects of gender, age, G-6-PD deficiency, sickle cell trait, HIV-1 status, and bacteremia. Comparison of alleles and genotype distribution among the clinical groups was performed using chi-square (X2) test. Multivariate logistic regression analysis revealed that relative to the wild type (CC genotype), there was no association between polymorphism in CD14 -C159T and susceptibility to SMA (CT, OR =0.75, CI =0.38-1.47, P=0.398, and TT, OR =1.23, CI =0.63-2.36 P=0.544). Further analysis revealed that the genotypic and allelic frequencies were comparable between SMA and the non-SMA (P=0.422). There was deviation from the Hardy Weinberg Equilibrium by the variant allele. The results from this study show that CD14 C-159T promoter polymorphisms are not associated with susceptibility to SMA in children from Siaya District, with alleleand genotype frequencies being comparable in the SMA and non-SMA groups. This study,contributes to the wealth of knowledge on association studies that try to reveal the pathogenesis of malaria. Further research on CD14 C-159T and its functionally related immune genesshould be conducted, to help decipher its exact role in severe malaria anemia. This would help in revealing the challenges associated with pathogenicity of Pfalciparum malaria in pediatric populations resident in P. jalciparum holoendemic transmission regions.