Association of the Glucocorticoid Receptor Gene Polymorphisms with TGF-β1 mRNA Expression in Childhood Asthma

Abstract

Background: Glucocorticoid (GC) is a fundamental drug used to treat asthma. GC binds to its corresponding receptor (GR) to formulate a complex that increases the production of anti-inflammatory factors and decreases the amount of pro-inflammatory mediators, covering many cytokines. GR is a nuclear receptor superfamily protein, encoded by NR3C1 gene. Studies suggest that polymorphisms of the NR3C1 gene contribute to a decreased response to GC for the treatment of asthma, even leading to drug-resistance. Also, TGF-β1 plays a central role in airway remodeling, GC significantly inhibits the production of TGF-β1, and TGF-β1 can induce GC resistance. Thus, it is possible that the polymorphisms of the NR3C1 gene can affect the expression of TGF-β1 mRNA and tissue remodeling. Objectives: This study evaluates the effect of polymorphisms (TthIII1, BclI, ER22/23EK, and N363S) of the NR3C1 GR gene on TGF-β1 mRNA expression in children with asthma. Methods: The samples of this study included 52 outpatients (age range: 6 - 14 years) with asthma referred to Huai’an First People’s Hospital, Nanjing Medical University, from January 2018 to June 2019. Meanwhile, 40 healthy volunteers were included as the control group. Results: The polymorphisms of the NR3C1 GR gene were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and TGF-β1 mRNA levels were measured by real-time reverse transcription (RT)-PCR. TthIII1 and TGF-β1 mRNA expression levels had significant (P = 0.011) correlations. But BclI showed no e effect on TGF-β 1 mRNA, N363S, and ER22/23EK had not been examined. Conclusions: According to the results, there was a relationship between single nucleotide polymorphisms (SNPs) of the NR3C1 gene and TGF-β1 mRNA in asthmatic children. TthIII1 CC and CT genotype have the strongest induction effect on the expression of TGF-1. The phenomenon suggests that SNPs may be involved in the asthma pathology.