Hemoglobinopathies, merozoite surface protein-2 gene polymorphisms, and acquisition of Epstein Barr virus among infants in Western Kenya

Perez K Olewe; Shehu Shagari Awandu; Elly O Munde; Samuel B Anyona; Evans Raballah; Asito S Amolo; Sidney Ogola; Erick Ndenga; Clinton O Onyango; Rosemary Rochford; Douglas J Perkins; Collins Ouma

doi:10.1186/s12885-023-11063-2

Hemoglobinopathies, merozoite surface protein-2 gene polymorphisms, and acquisition of Epstein Barr virus among infants in Western Kenya

BMC Cancer. 2023 Jun 20;23(1):566. doi: 10.1186/s12885-023-11063-2.

Authors

Perez K Olewe^{1

2}, Shehu Shagari Awandu¹, Elly O Munde^{2

3}, Samuel B Anyona^{2

4}, Evans Raballah^{2

5}, Asito S Amolo⁶, Sidney Ogola⁷, Erick Ndenga⁸, Clinton O Onyango², Rosemary Rochford⁹, Douglas J Perkins^{2

10}, Collins Ouma^{11

12

13}

Affiliations

¹ Department of Biomedical Sciences, School of Health Sciences, Jaramogi Oginga Odinga University of Science and Technology, Bondo, Kenya.
² University of New Mexico-Kenyan Global Health Programs Laboratories, Kisumu and Siaya, New Mexico, Kenya.
³ Department of Clinical Medicine, Kirinyaga University, Kerugoya, Kenya.
⁴ Department of Medical Biochemistry, School of Medicine, Maseno University, Maseno, Kenya.
⁵ Department of Medical Laboratory Sciences, School of Public Health Biomedical Science and Technology, Masinde Muliro University of Science and Technology, Kakamega, Kenya.
⁶ Department of Biological Sciences School of Biological, Physical, Mathematics, and Actuarial Sciences, Jaramogi Oginga Odinga University of Science and Technology, Bondo, Kenya.
⁷ Kenya Medical Research Institute - CGHR, Kisumu, Kenya.
⁸ Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, Kenya.
⁹ University of Colorado, Anshutz Medical Campus, Colorado, USA.
¹⁰ Center for Global Health, Internal Medicine, University of New Mexico, New Mexico, NM, USA.
¹¹ University of New Mexico-Kenyan Global Health Programs Laboratories, Kisumu and Siaya, New Mexico, Kenya. collinouma@yahoo.com.
¹² Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, Kenya. collinouma@yahoo.com.
¹³ Research and Innovations, Maseno University, Kisumu-Busia Road Private Bag, Maseno, Kenya. collinouma@yahoo.com.

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 strong selection pressure on sickle cell trait (SCT), alpha thalassemia (-α^3.7/αα), glucose-6-phosphate dehydrogenase (G6PD), and merozoite surface protein 2 (MSP-2) variants (FC27, 3D7) that confer reduced malarial disease severity. The current study tested the hypothesis that SCT, (-α^3.7/αα), G6PD mutation and (MSP-2) variants (FC27, 3D7) are associated with an early age of EBV acquisition.

Methods: Data on infant EBV infection status (< 6 and ≥ 6-12 months of age) 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. The 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 modeling was used to determine the relationship between the carriage of genetic variants and EBV acquisition.

Results: EBV acquisition for infants < 6 months was not associated with -α^3.7/αα (OR = 1.824, P = 0.354), SCT (OR = 0.897, P = 0.881), or G6PD [Viangchan (871G > A)/Chinese (1024 C > T) (OR = 2.614, P = 0.212)] and [Union (1360 C > 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 -α^3.7/αα (OR = 0.681, P = 0.442), SCT (OR = 0.513, P = 0.305), G6PD [(Viangchan (871G > A)/Chinese (1024 C > T) (OR = 0.640, P = 0.677)], [Mahidol (487G > A)/Coimbra (592 C > T) (OR = 0.948, P = 0.940)], [(Union (1360 C > 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 (-α^3.7/αα, SCT, and G6PD mutations) and in-utero exposure to MSP-2 were not associated with EBV acquisition in infants 0-12 months, novel G6PD variants were discovered in the population from western Kenya. To 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 from multiple sites adopting genome-wide analysis are required.

Keywords: Alpha thalassemia; EBV; G6PD mutations; MSP-2; SCT.

MeSH terms

Animals
Child
Epstein-Barr Virus Infections* / epidemiology
Epstein-Barr Virus Infections* / genetics
Hemoglobinopathies*
Herpesvirus 4, Human / genetics
Humans
Infant
Kenya / epidemiology
Malaria* / epidemiology
Malaria* / genetics
Malaria, Falciparum*
Merozoites
Polymorphism, Genetic

Abstract

MeSH terms

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