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

• Published in: Surgery today (Tokyo, Japan) Japan), 2019-03, Vol.49 (3), p.268-274
• Main Authors: Yamamoto, Haruchika, Sugimoto, Seiichiro, Tanaka, Shin, Kurosaki, Takeshi, Otani, Shinji, Yamane, Masaomi, Taira, Naruto, Oto, Takahiro, Toyooka, Shinichi
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Child; Chronic Disease; Female; Glucocorticoids - metabolism; Glucocorticoids - therapeutic use; Humans; Lung Transplantation - mortality; Male; Medicine; Medicine & Public Health; Middle Aged; Original Article; Polymorphism, Single Nucleotide - genetics; Primary Graft Dysfunction - genetics; Primary Graft Dysfunction - prevention & control; Receptors, Glucocorticoid - genetics; Surgery; Surgical Oncology; Survival Rate; Time Factors; Total Lung Capacity - genetics; Young Adult
• ISSN: 0941-1291; 1436-2813
• DOI: 10.1007/s00595-018-1717-9

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.