title: Strong association of a tumor necrosis factor-alpha promoter allele with cerebral malaria in Myanmar.
abstract: To investigate the host genetic factors affecting the clinical course of falciparum malaria, polymorphism of the tumor necrosis factor-alpha (TNF-alpha) promoter region was analyzed in patients with cerebral malaria. Two hundred and forty-three Myanmar patients with falciparum malaria at Mae Sot Malaria clinic and Mae Sot General Hospital located at the border between Thailand and Myanmar, were included in this study. Among the patients (128 from Karen, 115 from Burma), 200 were uncomplicated and 43 had cerebral malaria. The TNF-alpha 5'- flanking region showed biallelic polymorphic sites at -238, -308, -857, -863, -1031, and there were 7 alleles (TNFP-A, B, C, D, M1, M4, M7) found in the patients from Myanmar. We found that the TNFP-D allele was significantly associated with cerebral malaria in the populations from Karen (Pc<0.0001, OR=124.86) and Burma (Pc<0.0001, OR=34.50). TNFP-D showed no significant linkage disequilibrium with any alleles of HLA-B or HLA-DRB1, suggesting that TNFP-D was primarily associated with cerebral malaria in Myanmar.
authors.affiliation: Department of Medical Zoology, Saitama Medical School, Saitama, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Ubalee
authors.forename: F
authors.initials: F
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: O
authors.initials: O
authors.lastname: Tasanor
authors.forename: Y
authors.initials: Y
authors.lastname: Wattanagoon
authors.forename: R
authors.initials: R
authors.lastname: Ruangweerayut
authors.forename: K
authors.initials: K
authors.lastname: Na-Bangchang
authors.forename: J
authors.initials: J
authors.lastname: Karbwang
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: T
authors.initials: T
authors.lastname: Kanda
authors.forename: K
authors.initials: K
authors.lastname: Hirayama
mesh_terms: D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D015810:Linkage Disequilibrium; D016779:Malaria, Cerebral / Q000235:genetics* / Q000276:immunology; D002052:Myanmar; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D014409:Tumor Necrosis Factor-alpha