A single-nucleotide polymorphism in a gene modulating glucocorticoid sensitivity is associated with the decline in total lung capacity after lung transplantation

Surg Today. 2019 Mar;49(3):268-274. doi: 10.1007/s00595-018-1717-9. Epub 2018 Sep 18.

Abstract

Purpose: Glucocorticoids are used to prevent chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). Our study was aimed at assessing the association between the glucocorticoid-induced transcript 1 gene (GLCCI1) variant, which modulates glucocorticoid sensitivity, and the postoperative lung function and development of CLAD after LT.

Methods: A total of 71 recipients of LT were genotyped for the GLCCI1 variant (rs37972) and divided into three groups: the homozygous mutant allele (TT) group, the heterozygous mutant allele (CT) group, and the wild-type allele (CC) group. The results of pulmonary function tests were compared with the postoperative baseline values.

Results: The total lung capacity (TLC) in the TT group was significantly lower than that in the CC group at 3 years after LT (P = 0.029). In the recipients of cadaveric LT, the TLC and forced expiratory volume in 1 s in the TT group were significantly lower than those in the CC groups, resulting in a significant worse CLAD-free survival at 3 years after LT (P = 0.016).

Conclusion: The GLCCI1 variant was associated with a significant decrease of the TLC at 3 years after LT and the development of CLAD at 3 years, especially in patients undergoing cadaveric LT.

Keywords: Chronic lung allograft dysfunction; Glucocorticoid; Lung transplantation; Single-nucleotide polymorphism; Total lung capacity.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Chronic Disease
  • Female
  • Glucocorticoids / metabolism*
  • Glucocorticoids / therapeutic use
  • Humans
  • Lung Transplantation* / mortality
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Primary Graft Dysfunction / genetics*
  • Primary Graft Dysfunction / prevention & control
  • Receptors, Glucocorticoid / genetics*
  • Survival Rate
  • Time Factors
  • Total Lung Capacity / genetics*
  • Young Adult

Substances

  • GLCCI1 protein, human
  • Glucocorticoids
  • Receptors, Glucocorticoid