Abstract
BackgroundTuberculosis remains a global public health problem. Genetic polymorphisms may affect the susceptibility, clinical characteristics, and adverse drug reactions of patients with TB. The present study aimed to examine the association of single nucleotide polymorphisms of lncRNA‐HNF1B‐3:1 with the clinical manifestation of TB in a Western Chinese population.MethodA total of 526 tuberculosis patients and 561 healthy subjects were recruited in Western China. The correlation between lnc‐HNF1B‐3:1 polymorphism and tuberculosis susceptibility was investigated. Moreover, the influence on adverse drug reactions following treatment was explored. A total of 7 SNPs within the lnc‐HNF1B‐3:1 locus was genotyped by the improved multiplex ligation detection reaction method.ResultsNo significant associations were noted between TB susceptibility and the presence of all 7 SNPs of the lnc‐HNF1B‐3:1 as determined by single‐locus analysis (All P > .05). The AA genotype of rs12939622 (in the dominant model) and the AA genotype of rs4262994 (in the recessive model) caused increased susceptibility of the subjects to fever (P < .001 and P = .008, respectively). The Rs2542670 G allele was associated with increased risk of thrombocytopenia, leukopenia, and chronic kidney damage following drug administration (P = .007, .029, .003, respectively).ConclusionThe present study reported for the first time that the rs12939622, rs4262994 and rs2542670 genotypes in lnc‐HNF1B‐3:1 locus may influence the clinical manifestations of tuberculosis.
Highlights
Tuberculosis (TB) is an ancient human disease that may have evolved with modern human populations over thousands of years.[1]
In the pres‐ ent study, we genotyped 7 single nucleotide polymorphisms (SNPs) within lnc‐HNF1B‐3:1 among 526 tuberculosis cases and 561 healthy subjects in order to analyze the association between lnc‐HNF1B‐3:1 polymorphisms and the clinical characteristics of active tuberculosis patients
A previous study demonstrated that the CD244 signaling pathway exhibited a posi‐ tive correlation with high expression levels of long non‐ coding RNAs (lncRNAs)‐BC050410 in CD8+ T cells stimulated during Mycobacterium tuberculosis (MTB) infection.[24]
Summary
Tuberculosis (TB) is an ancient human disease that may have evolved with modern human populations over thousands of years.[1]. With the continuous improvement of high‐throughput genotyp‐ ing and sequencing technologies, genome‐wide association stud‐ ies (GWAS) have enabled in the past decades the identification of the genetic factors responsible for the development of complex diseases.[9] In addition, approximately half of the identified disease‐ associated single nucleotide polymorphisms (SNPs) do not include protein‐coding genes.[10] In 2012, Thye et al[11] reported a novel as‐ sociation between the rs2057178 polymorphism of chromosome 11p13 with resistance to TB. The side effects are the leading cause (57%) of unsuccessful response to TB treatment of patients in the Centers for Disease Control in China.[15] it is of great importance to investigate the susceptibility of the SNP loci that may be involved in the development of ADRs. In the pres‐ ent study, we genotyped 7 SNPs within lnc‐HNF1B‐3:1 among 526 tuberculosis cases and 561 healthy subjects in order to analyze the association between lnc‐HNF1B‐3:1 polymorphisms and the clinical characteristics of active tuberculosis patients
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