Association of TNF-Alpha, MBL2, NOS2, and G6PD with Malaria Outcomes in People in Southern Ghana

BACKGROUND: One major issue that has set back the gains of the numerous malaria control interventions that national malaria control programs have implemented is asymptomatic malaria. Certain host genetic factors are known to influence symptomatic malaria; however, not much is known about how host genetics influences the acquisition of asymptomatic malaria. METHODS: Genomic DNA was extracted from whole blood collected from 60 symptomatic and 149 nonfebrile (asymptomatic, N = 109, and uninfected, N = 40) volunteers aged between 2 and 69 years from a high (Obom) and a low (Asutsuare) malaria transmission setting in Southern Ghana. Restriction fragment length polymorphism (RFLP) was used to determine polymorphisms at the MBL2 54, TNF-α 308, NOS2 954, and G6PD 202/376 gene loci. RESULTS: Polymorphisms at the MBL2 54 and TNF-α 308 loci were significantly different amongst the three categories of volunteers in both Asutsuare (p = 0.006) and Obom (p=0.05). In Asutsuare, a low malaria transmission area, the allele G has significantly higher odds (3.15) of supporting asymptomatic malaria as against symptomatic malaria. There were significantly higher odds of TNF-α genotype GA being associated with symptomatic malaria as against asymptomatic malaria in both sites, Obom (p=0.027) and Asutsuare (p=0.027). The allele B of the G6PD gene was more prevalent in symptomatic rather than asymptomatic parasite-infected individuals in both Obom (p=0.001) and Asutsuare (p=0.003). CONCLUSION: Individuals in Southern Ghana carrying the TNF-α 308 GA genotype are more likely to exhibit symptoms of malaria when infected with the malaria parasite as opposed to harboring an asymptomatic infection. Also, the B allele of the G6PD gene is likely to prevent a P. falciparum-infected person from exhibiting symptoms and thereby promote asymptomatic parasite carriage.