Significant association of longer forms of CCTTT Microsatellite repeat in the inducible nitric oxide synthase promoter with severe malaria in Thailand.
A CCTTT microsatellite repeat in the inducible nitric oxide synthase (iNOS) promoter was analyzed among 256 adult patients with severe Plasmodium falciparum malaria and 179 adult patients with mild malaria living in northwestern Thailand. Genotypes with longer forms of the CCTTT repeat (alleles of > or =15 repeats) were significantly associated with severe malaria (odds ratio [OR], 2.14; P=.0029, chi(2) test). More interestingly, the summed repeat number of both microsatellite alleles in an individual was found to be a significant risk factor for severe malaria (OR, 1.11; logistic regression analysis, P=.0041). The single nucleotide substitution, -954G-->C, in the iNOS promoter was rare in Thai patients with malaria. No variations were detected in the iNOS promoter region containing functional NF-kappaB elements at -5.2, -5.5, -5.8, and -6.1 kb upstream of the iNOS transcriptional start site. Thus, a CCTTT repeat in the iNOS promoter may play a key role in the pathogenesis of severe malaria.
Ohashi
Jun
J
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Japan. juno@m.u-tokyo.ac.jp
Naka
Izumi
I
Patarapotikul
Jintana
J
Hananantachai
Hathairad
H
Looareesuwan
Sornchai
S
Tokunaga
Katsushi
K
D000328:Adult; D000483:Alleles; D000818:Animals; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D016779:Malaria, Cerebral / Q000235:genetics / Q000469:parasitology / Q000503:physiopathology; D016778:Malaria, Falciparum / Q000235:genetics / Q000469:parasitology / Q000503:physiopathology*; D018895:Microsatellite Repeats / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010963:Plasmodium falciparum / Q000472:pathogenicity; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D013785:Thailand
D016328:NF-kappa B; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II