Association study of TRAP1 gene polymorphisms with susceptibility and glucocorticoids efficacy of systemic lupus erythematosus

Gene. 2018 Sep 10:671:117-126. doi: 10.1016/j.gene.2018.05.109. Epub 2018 May 31.

Abstract

New functions of tumor necrosis factor receptor-associated protein 1 (TRAP1) have been investigated recently. This study explored if TRAP1 gene polymorphisms in patients with systemic lupus erythematosus (SLE) are associated with disease susceptibility and the efficacy of glucocorticoids (GCs). A case control study was performed to explore the association between TRAP1 gene polymorphisms and susceptibility to SLE, then the SLE patients included in the case control study were followed to investigate the relationship between TRAP1 gene polymorphisms and efficacy of GCs. We also compared the improvement in health related quality of life (HRQOL) of patients among different genotypes of TRAP1 gene. The Benjamini-Hochberg (BH) method was used to correct for multiple comparison. In case control study, the significant association between rs8055172 and the susceptibility to SLE was discovered in the dominant model (p = 3.54 × 10-7), which is further supported by the different distributions of haplotype TT and TC of rs2072379 and rs8055172 (p = 4.26 × 10-4 and p = 6.93 × 10-9). In the dominant model, rs3751842 and rs1639150 may be associated with fever of SLE patients (p = 0.035 and p = 0.028), while rs2072379 and rs12597773 related to oral ulcers (p = 0.021) and hematologic disorder (p = 0.035) respectively. In the follow-up study, rs6500552 showed a significant relationship with the efficacy of GCs in SLE patients in the dominant model (p = 0.004). Besides, rs3794701 was associated with the improvement in role-emotional (RE) of SLE patients in dominant model (p = 0.029). The results supported that TRAP1 gene polymorphisms may be associated with susceptibility to SLE and efficacy of GCs in SLE patients.

Keywords: Glucocorticoids; HRQOL; Polymorphism; Systemic lupus erythematosus; TRAP1.

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Glucocorticoids / therapeutic use*
  • HSP90 Heat-Shock Proteins / genetics*
  • Humans
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Quality of Life
  • Treatment Outcome
  • Young Adult

Substances

  • Glucocorticoids
  • HSP90 Heat-Shock Proteins
  • TRAP1 protein, human