Nitric oxide synthase type 2 promoter polymorphisms, nitric oxide production, and disease severity in Tanzanian children with malaria

Nitric oxide (NO) plays an important role in host resistance to infection w ith a variety of organisms. Two recent reports from Gabon and Gambia identi fied associations of malaria disease severity with the inducible NO synthas e (NOS2) promoter G-954C and short allele (<11 repeats) pentanucleotide mic rosatellite polymorphisms, respectively. It was postulated that there would be a correlation of these polymorphisms with malaria disease severity and with measures of NO production in our cohort of Tanzanian children with mal aria. In Tanzanian children, 15% were heterozygous or homozygous for the G- 954C polymorphism, and 13% had the short-allele microsatellite polymorphism . There was no significant correlation of either polymorphism with disease severity or with measures of NO production and NOS2 expression. Black and w hite Americans differed significantly in the frequencies of these polymorph isms. The various association of these gene polymorphisms with malaria seve rity in different populations underscores the complexity of host resistance to malaria.