Genetic polymorphism of human leucocyte antigen and susceptibility to multidrug‐resistant and rifampicin‐resistant tuberculosis in Han Chinese from Hubei Province

Summary We determined the high‐resolution allele and haplotype frequencies at the human leucocyte antigen ( HLA )A, B and DRB 1 loci in the Han population of Hubei province, the TB endemic area of Central China, with pulmonary tuberculosis ( PTB ), and established the relationship between HLA ‐A, B and DRB 1 alleles as well as haplotypes and susceptibility to multidrug‐resistant and rifampicin‐resistant tuberculosis ( MDR / RR ‐ TB ). Blood samples were drawn from 174 patients with MDR / RR ‐ TB and 838 patients with drug‐susceptible PTB in ethnic Han population from Hubei province (central China). Four‐digit allele genotyping of HLA‐ A, B and DRB1 loci was performed using polymerase chain reaction with sequence‐specific oligonucleotide probes (PCR‐ SSOP). The allele and haplotype frequencies of HLA ‐A, B and DRB 1 were determined and compared between patients with MDR / RR ‐ TB and patients with drug‐susceptible PTB . Statistical analysis of the generated data indicated no departure from expectation of Hardy–Weinberg equilibrium ( HWE ) at all loci of the control group. Multivariate analysis identified allele DRB 1*08:01 ( p  < .0001; OR  = 174.5, 95% CI 15.3–1987.2) as independent predictor of MDR / RR ‐ TB , except for old age ( p  < .0001; OR  = 10. 9, 95% CI 7.6–15.8), previous treatment history ( p  < .0001; OR  = 11.0, 95% CI 7.2–16.7) and poor compliance to treatment ( p  < .0001; OR  = 12.9, 95% CI 8.4–20.0). While in the subgroup of new TB cases, DRB 1*08:01 ( p  < .0001; OR  = 80.3, 95% CI 7.0–917.1) and older age ( p  < .0001; OR  = 3.9, 95% CI 2.4–6.4) were independent susceptibility factors for primary MDR / RR ‐ TB . Our results suggest that a combination of clinical and host genetic information about tuberculosis patients may contribute to prediction and early detection of MDR / RR ‐ TB .