Inducible Nitric Oxide Synthase 2 Promoter Polymorphism and Malaria Disease Severity in Children in Southern Ghana

Abstract

Objective We assessed the association of mutant allele frequencies of nitric oxide synthase 2 (NOS2) gene at two SNPs (-954 and -1173) with malaria disease severity in children from a malaria endemic area in Southern Ghana. Method Using children recruited at the hospital, assigned into clinical subgroups of uncomplicated and severe malaria and matching with their ªhealthy controlº counterparts, we designed a case control study. Genomic DNA was extracted and genotyping using Restriction Fragment Polymorphism was done. Result A total of 123 malaria cases (91 uncomplicated, 32 severe) and 100 controls were sampled. Their corresponding mean Hbs were 9.6, 9.3 and 11.2g/dl and geometric mean parasite densities of 32097, 193252 and 0 parasites/ml respectively. Variant allele frequencies varied from 0.09 through 0.03 to 0.12 for G-954C and 0.06 through 0.03 to 0.07 for C-1173T in the uncomplicated, severe and healthy control groups respectively. There was a strong linkage disequilibrium between the two alleles (p<0.001). For the -954 position, the odds of developing severe malaria was found to be 2.5 times lower with the carriage of a C allele compared to those without severe malaria (χ2; p< 0.05) though this isn't the case with -1173. Conclusion The carriage of a mutant allele in the -954 NOS2 gene may have a protective effect on malaria among Southern Ghanaian children.