Genetic polymorphism and transcriptional regulation of CREBBP gene in patient with diffuse large B-cell lymphoma

Biosci Rep. 2019 Aug 13;39(8):BSR20191162. doi: 10.1042/BSR20191162. Print 2019 Aug 30.

Abstract

In the present study, we aim to examine the relationship between genetic polymorphism and transcriptional expression of cyclic AMP response element binding protein (CREBBP) and the risk of diffuse large B-cell lymphoma (DLBCL). Two hundred and fifty healthy individuals and 248 DLBCL patients participated in the present study. The CREBBP rs3025684 polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The mRNA expression of CREBBP was tested by the real-time quantitative PCR (RT-qPCR). The allele A frequency of CREBBP rs3025684 in DLBCL patients was obviously higher than that of controls (P=0.01). No significant difference was detected between CREBBP rs3025684 polymorphism and clinical characteristics of DLBCL patients when subgrouped according to different parameters. The results demonstrated that the allele A of CREBBP rs3025684 increased the susceptibility to DLBCL (P=0.004), with a worse overall survival (OS) rate (P=0.002), a worse progression-free survival (PFS) rate (P=0.033) and poor prognosis (P=0.003) in DLCBL patients. Furthermore, the expression of CREBBP mRNA was considerably decreased in DLBCL patients as compared with controls (P<0.001), and the expression in patients with GG genotype was up-regulated in comparison with patients with GA and AA genotype (P=0.016 and P=0.001, respectively). However, no statistical differences were found in OS (P=0.201) and PFS (P=0.353) between the lower CREBBP mRNA level subgroup and higher CREBBP mRNA level subgroup. These data suggested that the CREBBP gene may be an important prognostic factor in DLBCL patients and perform an essential function in the development of DLBCL.

Keywords: CREBBP; DLBCL; expression; polymorphism.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • CREB-Binding Protein* / biosynthesis
  • CREB-Binding Protein* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Frequency
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Lymphoma, Large B-Cell, Diffuse* / metabolism
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins* / biosynthesis
  • Neoplasm Proteins* / genetics
  • Polymorphism, Restriction Fragment Length*
  • Transcription, Genetic*

Substances

  • Neoplasm Proteins
  • CREB-Binding Protein
  • CREBBP protein, human