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

We determined the high-resolution allele and haplotype frequencies at the human leucocyte antigen (HLA)A, B and DRB1 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 DRB1 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 DRB1 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 DRB108:01 (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, DRB108:01 (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.