ASSOCIATION OF AN HLA-DQ ALLELE WITH CLINICAL TUBERCULOSIS

Context.-Although tuberculosis (TB) is the leading worldwide cause of death due to an infectious disease, the extent to which progressive cl inical disease is associated with genetic host factors remains undefin ed. Objective.-To determine the distribution of HLA antigens and the f requency of 2 alleles of the tumor necrosis factor alpha (TNF-alpha) g ene in unrelated individuals with clinical TB (cases) compared with in dividuals with no history of clinical TB (controls) in a population wi th a high prevalence of TB exposure.Design.-A 2-stage, case-control mo lecular typing study conducted in 1995-1996.Setting.-Three district ho spitals in Svay Rieng Province in rural Cambodia. Patients.-A total of 78 patients with clinical TB and 49 controls were included in the fir st stage and 48 patients with TB and 39 controls from the same area an d socioeconomic status were included in the second stage. Main Outcome Measures.-Presence of HLA class I and class II alleles determined by sequence-specific oligonucleotide probe hybridization and presence of 2 TNF-alpha alleles determined by restriction fragment length polymorp hism analysis. Results.-In the first stage, 7 DQB10503 alleles were d etected among 156 alleles derived from patients with TB, whereas no DQ B10503 alleles were found among the 98 alleles derived from controls (P=.04), There was no detectable difference in the distribution of the 2 TNF-alpha alleles in patients with TB compared with controls, In th e second stage, we tested for the presence of a single variable, the D QB10503 allele, and found 9 DQB1*0503 alleles among 96 alleles derive d from patients with TB and no DQB10503 alleles among 78 alleles in c ontrols (P=.005), Conclusions.-The HLA-DQB10503 allele is significant ly associated with susceptibility to TB in Cambodian patients and, to our knowledge, is the first identified gene associated with developmen t of clinical TB.