Severity of malaria in relation to a complement receptor 1 polymorphism: A case-control study

Background: Studies on the relationship between complement receptor 1 (CR1) polymorphisms in exon 29 encoding the Knops blood group antigens (Swain-Langley (Sl) and McCoy (McC)) and outcome of clinical malaria have produced inconsistent results. Methods: Blood samples from Ghanaian children (n=150) aged 1-12 years with complicated and uncomplicated malaria were genotyped for the Sl and McC blood group alleles by polymerase chain reaction and restriction fragment length polymorphism. Effect of Sl and McC genotypes on the clinical outcome of malaria was evaluated using logistic regression. Results: McCa/b genotype was significantly associated with more than two-fold increased susceptibility for severe malaria (OR=2.31; 95% CI: 1.03-5.20, P=0.043). However, McCb/b was associated with an 88% reduced risk of severe malaria (OR=0.12; 95% CI: 0.02-0.64, P=0.013). In contrast, there was no significant association between severe malaria and Sl1/1, Sl1/2, Sl2/and McCa/a genotypes. There was a trend towards decreased susceptibility to both cerebral malaria (CM) (OR=0.13; 95% CI: 0.02-1.15, P=0.07) and severe malarial anaemia (SA) (OR=0.14; 95% CI: 0.02-1.19, P=0.07) for McCb/b genotype when compared with the McCa/a genotype. There were no significant associations between Sl1/2 or Sl2/2 genotype and CM or SA when compared with Sl1/1 genotype. Conclusions: McCa/b was associated with increased susceptibility to severe malaria and McCb/b associated with reduced risk of severe malaria. Further studies with large sample size in other malaria endemic regions in Africa are warranted to confirm these findings.