Genes of the class II and class III major histocompatibility complex are associated with typhoid fever in Vietnam.
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.
Dunstan
S J
SJ
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, SW7 2AZ, United Kingdom. s.dunstan@ic.ac.uk
Stephens
H A
HA
Blackwell
J M
JM
Duc
C M
CM
Lanh
M N
MN
Dudbridge
F
F
Phuong
C X
CX
Luxemburger
C
C
Wain
J
J
Ho
V A
VA
Hien
T T
TT
Farrar
J
J
Dougan
G
G
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
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