Significance of LncRNA CASC8 genetic polymorphisms on the tuberculosis susceptibility in Chinese population.

Guoye Liu,Hong Yan,Binwu Ying,Rui Xia,Zhiqiang Wang,Qian Wang

doi:10.1002/jcla.23234

Abstract

BackgroundTuberculosis remains an important disease threatening the security of public health, and no effective targets have been found for the immunological diagnosis or therapy of tuberculosis. The aim of this study was to explore the associations between lncRNA CASC8 genetic polymorphism and tuberculosis risk.MethodA total of 900 tuberculosis patients and 1534 healthy individuals in the Western Chinese Han population were recruited for our study. Candidate SNPs of CASC8 were initially filtered by importing the 1000 genomes database into Haploview, and subsequently genotyped using modified multiplex ligation detection reactions.ResultsThe lncRNA CASC8 genetic variant rs7836840 was associated with an increased tuberculosis risk with a P‐value of .034, but .134 after Bonferroni correction. Using subtype analysis, the C allele in rs7836840 showed a significant association with tuberculosis susceptibility (OR = 1.196, 95% CI = 1.05‐1.362, P = .02739 after Bonferroni correction). Patients carrying genotype AG and GG of rs7825118 and rs9297758 exhibited lower Hb concentrations (P = .006) and neutrophil counts (P = .015), respectively, while genotype AG and AA in rs6981424 demonstrated higher levels of ALT (P = .005) and AST (P = .033) in a dominant model, which were consistent with a tendency toward increased TB risk.ConclusionsThis study was the first to explore the association between lncRNA CASC8 polymorphisms and TB infection risk and clinical manifestations. Our results provide evidence that CASC8 may act as a biomarker for the progression of clinical tuberculosis.

Highlights

Tuberculosis (TB) caused by M tuberculosis (MTB) is a chronic communicable disease that remains one of the top 10 causes of death in the world and is the leading cause of death by a single infectious agent
An estimated 1.7 billion people are infected with MTB worldwide, only 5%-10% of latent tuberculosis infection (LTBI) individuals will go on to develop active TB.[2]
This indicates that host genetic factors, mainly associated with “candidate” genes, including the genes encoding human leukocyte antigen (HLA), killer immunoglobulin-like receptor (KIR), toll-like receptors (TLRs), cytokine/chemokines and their receptors, vitamin D receptor (VDR) and SLC11A1 play important roles in determining individual susceptibility to infectious TB.[3]

Summary

| INTRODUCTION

Tuberculosis (TB) caused by M tuberculosis (MTB) is a chronic communicable disease that remains one of the top 10 causes of death in the world and is the leading cause of death by a single infectious agent. Our research team previously reported the presence of differentially expressed lncRNA in peripheral blood mononuclear cells (PBMCs) in response to multidrug-resistant TB (MDR-TB) infection.[12] These data reveal that lncRNAs play important roles in TB infection, and we selected to investigate lncRNA polymorphisms and their association with human susceptibility to clinical TB. Fu et al[13] conducted microarray analysis to investigate differentially expressed lncRNA and mRNA genes in CD8+ T cells isolated from active TB group and healthy control group and recorded these profiles in the GEO database (GSE97530). Our study selected a set of SNPs within CASC8 among 900 tuberculosis cases and 1534 healthy controls in the Han Chinese population and systematically analyzed the associations between lncRNA polymorphisms and the occurrence and clinical characterization of TB infections

| METHODS AND MATERIALS

Findings

| DISCUSSION