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

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 "healthy control" 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.