Abstract
ObjectivesThe Liver X receptors (LXRs), Liver X receptor A (LXRA) and Liver X receptor B (LXRB), regulate lipid metabolism and antimicrobial response. LXRs have a crucial role in the control of Mycobacterium tuberculosis (M.tb). Lacking LXRs mice is more susceptibility to infection M.tb, developing higher bacterial burdens and an increase in the size and number of granulomatous lesions. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXRs and risk of tuberculosis.MethodsWe sequenced the LXRs genes to detect SNPs and to examine genotypic frequencies in 600 patients and 620 healthy controls to investigate for associations with tuberculosis (TB) in the Chinese Han population. DNA re-sequencing revealed eight common variants in the LXRs genes.ResultsThe G allele of rs1449627 and the T allele of rs1405655 demonstrated an increased risk of developing TB (p<0.001, p = 0.002), and the T allele of rs3758673, the T allele of rs2279238, and the C allele of rs1449626 in LXRA and the C allele of rs17373080, the G allele of rs2248949, and the C allele of rs1052677 in LXRB were protective against TB patients compared to healthy controls (p = 0.0002, p = 0.006, p<0.001, p = 0.004, p = 0.008, p = 0.003, respectively). All SNP genotypes were significantly associated with TB. An estimation of the frequencies of haplotypes revealed two potential risk haplotypes,GGCG in LXRB (p = 0.004,) and TTCG in LXRA (p<0.001, p = 0.004). Moreover, three protective haplotypes, TTAT and CCAT in LXRA and CATC in LXRB, were significantly “protective” (p = 0.008, p<0.001, p = 0.031) for TB. Furthermore, we determined that the LXRs SNPs were nominally associated with the clinical pattern of disease.ConclusionsOur study data supported that LXRs play a fundamental role in the genetic susceptibility to TB and to different clinical patterns of disease. Thus, further investigation is required in larger populations and in additional areas.
Highlights
The G allele of rs1449627 and the T allele of rs1405655 demonstrated an increased risk of developing TB (p,0.001, p = 0.002), and the T allele of rs3758673, the T allele of rs2279238, and the C allele of rs1449626 in Liver X receptor A (LXRA) and the C allele of rs17373080, the G allele of rs2248949, and the C allele of rs1052677 in Liver X receptor B (LXRB) were protective against TB patients compared to healthy controls (p = 0.0002, p = 0.006, p,0.001, p = 0.004, p = 0.008, p = 0.003, respectively)
One-third of the population is infected with Mycobacterium tuberculosis (M.tb) worldwide, which is the main etiological agent of tuberculosis (TB)
Liver X receptors (LXRs), Liver X receptor a (LXRA, NR1H3) and Liver X receptor b (LXRB, NR1H2), are a subset of nuclear receptor transcription factors that have emerged as master regulators of lipid [1,2], inflammation [3,4] and glucose metabolism [5,6,7,8,9]
Summary
One-third of the population is infected with Mycobacterium tuberculosis (M.tb) worldwide, which is the main etiological agent of tuberculosis (TB). M.tb is a prototypic intracellular macrophage pathogen, and resides for a long period of time to avoid recognition of the human immune system during clinical dormancy. The host protective immunity plays a pivotal role in the primary immune response and active immune response, which is central in inflammation processes. A large body of literature has indicated a role of LXRs in inflammation. LXRs, which are expressed in many immune cells, such as the dendritic cell [10,11], macrophage [12], and Lymphocyte, regulate network of genes that affect many aspects of the immune system [13,14]
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