Hemoglobinopathies, Merozoite Surface Protein-2 Gene Polymorphisms, and Acquisition of Epstein Barr Virus Among Infants in Western Kenya

Abstract

Background Epstein Barr virus (EBV)-associated endemic Burkitt's Lymphoma pediatric cancer is associated with morbidity and mortality among children resident in holoendemic Plasmodium falciparum regions in western Kenya. P. falciparum exerts a strong selection pressure on sickle cell trait (SCT), alpha thalassemia (-α3.7/αα), glucose-6-phosphate dehydrogenase (G6PD), and merozoite surface protein 2 (MSP-2) variants (FC27, 3D7) that confer reduced malarial disease severity Methods Data on infant EBV infection status (<6 and ≥6-12 months of ages) was abstracted from a previous longitudinal study. Archived infant DNA (n=81) and mothers DNA (n=70) samples were used for genotyping hemoglobinopathies and MSP-2. Presence of MSP-2 genotypes in maternal DNA samples was used to indicate infant in utero malarial exposure. Genetic variants were determined by TaqMan assays or standard PCR. Group differences were determined by Chi-square or Fisher’s analysis. Bivariate regression modelling was used to determine the relationship between carriage of genetic variants and EBV acquisition. Results EBV acquisition for infants <6 months was not associated with -α3.7/αα (OR=1.824, P =0.354), SCT (OR=0.897, P=0.881), or G6PD [Viangchan (871G>A)/Chinese (1024C>T) (OR=2.614, P=0.212)] and [Union (1360C>T)/Kaiping (1388G>A) (OR=0.321, P=0.295)]. There was no relationship between EBV acquisition and in utero exposure to either FC27 (OR=0.922, P=0.914) or 3D7 (OR=0.933, P=0.921). In addition, EBV acquisition in infants ≥6-12 months also showed no association with -α3.7/αα (OR=0.681, P=0.442), SCT (OR=0.513, P=0.305), G6PD [(Viangchan (871G>A)/Chinese (1024C>T) (OR=0.640, P=0.677)], [Mahidol (487G>A)/Coimbra (592C>T) (OR=0.948, P=0.940)], [(Union (1360C>T)/Kaiping (1388G>A) (OR=1.221, P=0.768)], African A (OR=0.278, P=0.257)], or in utero exposure to either FC27 (OR=0.780, P=0.662) or 3D7 (OR=0.549, P=0.241). Conclusion: Although hemoglobinopathies (-α3.7/αα, SCT, and G6PD mutations) and in utero exposure to MSP-2 was not associated with EBV acquisition in infants 0-12 months, novel G6PD variants were discovered in the population from western Kenya. To definitely establish that the known and novel hemoglobinopathies, and in utero MSP-2 exposure do not confer susceptibility to EBV, future studies with larger sample sizes are required.