Host polymorphisms and the incidence of malaria in Ugandan children.
Mutations in beta-globin, glucose-6-phosphate dehydrogenase, and promoters for tumor necrosis factor-alpha and inducible nitric oxide synthase (iNOS) were examined for associations with the incidence of symptomatic malaria in a cohort of 307 Ugandan children. After adjustment of incidence rates for age, water source, use of preventative measures, and proximity to mosquito breeding sites, glucose-6-phosphate dehydrogenase A- heterozygous females had a significantly higher incidence of malaria (incidence rate ratio [IRR] = 1.63, P = 0.03) and a trend towards higher parasite densities (37,100 versus 26,200 parasites/microL; P = 0.18) compared with wild-type children. Male hemizygotes had trends in the same direction. Heterozygotes for sickle hemoglobin had trends toward a lower incidence of malaria and lower parasite density at presentation. Heterozygotes for the iNOS promoter G954C polymorphism, but not other promoter polymorphisms, had a significantly lower incidence of malaria compared with wild-type children (IRR = 0.69, P = 0.05). Host polymorphisms appear to impact upon the incidence of uncomplicated malaria in Ugandan children.
Parikh
Sunil
S
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA. sunil@itsa.ucsf.edu
Dorsey
Grant
G
Rosenthal
Philip J
PJ
D002675:Child, Preschool; D005260:Female; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007223:Infant; D008288:Malaria / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012805:Sickle Cell Trait / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014454:Uganda / Q000453:epidemiology
D014409:Tumor Necrosis Factor-alpha; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II