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

Abstract

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 DRB1*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, DRB1*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.

Association between HLA-A*3201 allele and oxcarbazepine-induced cutaneous adverse reactions in Eastern Han Chinese population

“…[50]. The frequency of HLA-A*3201 was 1.11% in 90 Chinese Han from Beijing in the 1000 Genomes Dataset [51] and less than 1% in 1012 Chinese Han from Hubei Province, a middle part of China [52]. Thus, we propose that screening for HLA-A*3201 allele should be routinely conducted when considering administration of OXCs initially or in the face of AEDs adjustment.…”

Association Study of MBL2 Gene Polymorphisms and Risk of Tuberculosis in Southeast of Iran

“…Base on World Health Organization (WHO) Global Tuberculosis Report, tuberculosis with 7 million new cases and 1.2 million deaths annually is the second-leading cause of death around the world (Huang et al, 2016;World Health Organization, 2019). However, one third of the world's population is infected with Mtb, where most of them do not develop active tuberculosis and while 5-15% of infected individuals develop the clinical disease (Zhou et al, 2018). In Zahedan (the capital of Sistan and Baluchistan province), the incidence rate of TB is higher than in other regions of Iran and tuberculosis infection is one of the major public problems.…”