HLA-A Alleles Differentially Associate with Severity to Plasmodium falciparum Malaria Infection in Ibadan, Nigeria

Abstract

Human Leukocyte Antigen (HLA), particularly HLA-B and class II alleles have been differentially associated with disease 
outcomes in different populations following infection with the malaria Plasmodium falciparum. However, the effect of HLA-A 
on malaria infection and/or disease is not fully understood. Recently, HLA-A alleles have been suggested to play a role in the 
outcome of P. falciparum malaria infection in a Malian study. Herein, we investigated the association between HLA-A alleles 
and the outcome of malaria infection in children in Ibadan southwest Nigeria. HLA-A genotyping was performed on 393 children 
samples (DNA) using the sequence-based method. We compared genotype and allele frequencies data obtained from these 
Nigerian children; 176 with asymptomatic malaria infection (controls), 124 with uncomplicated malaria and 93 children with 
severe malaria (51 severe malarial anaemia and 42 cerebral malaria). We found a high frequency of HLA-A*36:01 (13.5%) in 
the entire studied population and also confirmed the high frequency of a previously reported allele of African origin (HLAA*30:01). After adjusting for age and parasite density, we found a significant association between HLA-A*20:01:01 (OR = 3.19, 
p < 0.001) and susceptibility to severe malarial anaemia. We also found significant associations between HLA-A* 29:02:01 (OR 
= 7.26, p = 0.008) and A* 66:02 (Or = 4.19, p = 0.03) and susceptibility to cerebral malaria. Our findings suggest that HLA-A 
alleles play a role in the outcome of malaria in children in Ibadan. These findings may help elucidate the molecular background 
of malaria resistance in the study population.