title: Human leukocyte antigen class I polymorphisms influence the mild clinical manifestation of Plasmodium falciparum infection in Ghanaian children.
abstract: A prospective study that included 429 children for active detection of mild malaria was conducted in a coastal region of Ghana to reveal whether the incidence of malaria is affected by human leukocyte antigen (HLA) polymorphism. During 12 months of follow-up, 85 episodes of mild clinical malaria in 74 individuals were observed, and 34 episodes among them were accompanied with significant parasitemia at >5000 infected red blood cells per cubic millimeter. Attributable and relative risks conferred by genetic factors in the HLA region were evaluated by comparison of the incidence in children, stratified by carrier status, of a given allele of HLA-A, -B, -DRB1 and TNFA promoter polymorphism. HLA-B*35:01 reduced the incidence by 0.178 events per person per year (0.060 versus 0.239 for B*35:01-positive and -negative subpopulations, respectively), and a relative risk of 0.25, which remained statistically significant after Bonferroni's correction for multiple testing (p(c) = 8.2 × 10(-5)). Further, HLA-B*35:01 and -B*53:01 exhibited opposite effects on the incidence of malaria with significant parasitemia. When parasite densities in different HLA carriers status were compared, HLA-A*01 conferred an increase in parasite load (p = 6.0 × 10(-7)). In addition, we found a novel DRB1 allele that appears to have emerged from DRB1*03:02 by single nucleotide substitution.
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamazaki
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
authors.forename: Michael
authors.initials: M
authors.lastname: Ofori
authors.forename: Hitomi
authors.initials: H
authors.lastname: Horie
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Gideon
authors.initials: G
authors.lastname: Helegbe
authors.forename: Akiko
authors.initials: A
authors.lastname: Takaki
authors.forename: Kazunari
authors.initials: K
authors.lastname: Ishii
authors.forename: Ahmeddin Hassan
authors.initials: AH
authors.lastname: Omar
authors.forename: Bartholomew D
authors.initials: BD
authors.lastname: Akanmori
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirayama
mesh_terms: D000483:Alleles; D044383:Black People; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D005869:Ghana / Q000453:epidemiology; D015234:HLA-A Antigens / Q000032:analysis / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000032:analysis / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000032:analysis / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D015994:Incidence; D007962:Leukocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D016778:Malaria, Falciparum / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000469:parasitology / Q000503:physiopathology; D008297:Male; D059208:Parasite Load; D010641:Phenotype; D010963:Plasmodium falciparum / Q000502:physiology*; D011110:Polymorphism, Genetic / Q000276:immunology; D011446:Prospective Studies; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000276:immunology
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D059811:HLA-DRB1 Chains; D014409:Tumor Necrosis Factor-alpha