title: Genes of the class II and class III major histocompatibility complex are associated with typhoid fever in Vietnam.
abstract: The influence of genes of the major histocompatibility complex (MHC) class II and class III loci on typhoid fever susceptibility was investigated. Individuals with blood culture-confirmed typhoid fever and control subjects from 2 distinct geographic locations in southern Vietnam were genotyped for HLA-DRB1 and HLA-DQB1 alleles, the gene that encodes tumor necrosis factor (TNF)-alpha (TNFA [-238] and TNFA [-308]), the gene that encodes lymphotoxin-alpha, and alleles of the TNF-alpha microsatellite. HLA-DRB1*0301/6/8, HLA-DQB1*0201-3, and TNFA*2 (-308) were associated with susceptibility to typhoid fever, whereas HLA-DRB1*04, HLA-DQB1*0401/2, and TNFA*1 (-308) were associated with disease resistance. The frequency of all possible haplotypes of the 3 individually associated loci were estimated and were found to be significantly different in typhoid case patients and control subjects (chi2=55.56, 32 df; P=.006). Haplotypes that were either protective (TNFA*1 [-308].DRB1*04) or predisposed individuals to typhoid fever (TNFA*2 [-308].DRB1*0301) were determined. This report identifies a genetic association in humans between typhoid fever and MHC class II and III genes.
authors: Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, SW7 2AZ, United Kingdom. s.dunstan@ic.ac.uk
authors: S J
authors: SJ
authors: Dunstan
authors: H A
authors: HA
authors: Stephens
authors: J M
authors: JM
authors: Blackwell
authors: C M
authors: CM
authors: Duc
authors: M N
authors: MN
authors: Lanh
authors: F
authors: F
authors: Dudbridge
authors: C X
authors: CX
authors: Phuong
authors: C
authors: C
authors: Luxemburger
authors: J
authors: J
authors: Wain
authors: V A
authors: VA
authors: Ho
authors: T T
authors: TT
authors: Hien
authors: J
authors: J
authors: Farrar
authors: G
authors: G
authors: Dougan
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D006650:Histocompatibility Testing; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics*; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014435:Typhoid Fever / Q000453:epidemiology / Q000235:genetics*; D014744:Vietnam / Q000453:epidemiology
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D000949:Histocompatibility Antigens Class II; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha