Human genetic polymorphisms and asymptomatic Plasmodium falciparum malaria in Gabonese schoolchildren.
Several studies have focused their attention on the relationship between host genetic factors and susceptibility/resistance to severe malaria. However, there is a paucity of information concerning the role of host genetic factors in asymptomatic malaria, a form of low-grade Plasmodium falciparum infection without clinical symptoms. We investigated in this study the potential relationship between the host (human) genetic polymorphisms (glucose-6-phosphate dehydrogenase [G6PD], mannose binding lectin [MBL], tumor necrosis factor alpha [TNFalpha](-308) and (-238), and nitric oxide synthase 2 [NOS2](-954)) and the prevalence and profile of asymptomatic P. falciparum infection in 158 Gabonese schoolchildren. We found that G6PD A- heterozygous females (18 of 74) have a low prevalence of asymptomatic malaria (38.9% versus 67.3%; P = 0.03, by chi-square test). Children heterozygous for TNFalpha(-238) (25 of 156) carry high number of diverse infecting parasite genotypes (2.5 versus 1.99; variance F = 3.05). No statistically significant association was found between MBL, TNFalpha(-308), or NOS2 polymorphisms and asymptomatic malaria. Upon combining our data on asymptomatic forms with those from the literature for others forms, we conclude that G6PD A- heterozygous females are protected against all forms of P. falciparum malaria, and that the TNFalpha(-238A) allele confers protection against clinical malaria.
Mombo
Landry-Erik
LE
Centre International de Recherches Médicales de Franceville, Franceville, Gabon. lemombo@yahoo.com
Ntoumi
Francine
F
Bisseye
Cyrille
C
Ossari
Simon
S
Lu
Chang Yong
CY
Nagel
Ronald L
RL
Krishnamoorthy
Rajagopal
R
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D002648:Child; D003430:Cross-Sectional Studies; D017931:DNA Primers; D019353:Endemic Diseases; D005260:Female; D005681:Gabon / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010963:Plasmodium falciparum / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D015800:Protozoan Proteins / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000953:Antigens, Protozoan; D017931:DNA Primers; D037601:Mannose-Binding Lectin; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; C065974:merozoite surface protein 2, Plasmodium; D005954:Glucosephosphate Dehydrogenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II