Correlation between polymorphisms of the NR3C1 gene and glucocorticoid effectiveness in patients with pemphigus vulgaris

Si-Yue Fang,Chun-Lei Li,Hong Hua,Xiao-Song Liu,Feng Chen

doi:10.1038/s41598-017-12255-0

Abstract

sGlucocorticoid (GC) resistance is the major obscule in the treatment of pemphigus vulgaris (PV) for both patients and clinicans with unclear mechanism. A hypotheis for this resistance is the mutations or polymorphisms present in the nuclear receptor subfamily 3, group C, member 1 (NR3C1) gene that encodes receptors for steroid hormones. This study aimed to investigate the association between NR3C1 gene polymorphisms and GC effectiveness in PV patients. 94 PV patients (64 GC-sensitive and 30 GC-resistant) and 100 healthy volunteers were enrolled in this case-control study. The genotyping of single nucleotide polymorphisms (SNPs) in BCL1, Arg23Lys, Asn363Ser 1548 t-insert, and le747Met, together with tag-SNP sites of the NR3C1 gene were evaluated. No significant differences were observed in genotypic and allelic frequencies of the 16 SNPs between PV patients and healthy volunteers. However, SNPs rs 11745958 C/T (OR: 8.95) and rs17209237 A/G (OR: 4.07) may be associated with an increased risk of GC resistance, while rs 33388 A/T (OR: 0.45) and rs7701443 A/G (OR: 0.51) may indicate a decreased risk of GC resistance in PV patients. NR3C1 gene variation may be associated with GC resistance in PV patients. More extensive genetic analyses and mechanistic analysis are required for further exploration.

Highlights

Pemphigus is a rare autoimmune disorder characterized by extensive blistering and erosions on the skin and mucosa caused by autoantibodies against desmoglein-1 (Dsg) and/or −3, which are major components of desmosomes; this damage leads to the histological observation of the detachment of epidermal cells[1]
This study aimed to evaluate the correlation between single nucleotide polymorphisms (SNPs) of the NR3C1 gene and GC resistance in Pemphigus vulgaris (PV) patients
The remaining 11 SNP sites in the control group were in Hardy-Weinbery equilibrium (HWE) (P > 0.05)

Summary

Introduction

Pemphigus is a rare autoimmune disorder characterized by extensive blistering and erosions on the skin and mucosa caused by autoantibodies against desmoglein-1 (Dsg) and/or −3, which are major components of desmosomes; this damage leads to the histological observation of the detachment of epidermal cells[1]. Pemphigus vulgaris (PV) is one of the major forms of pemphigus, which affects the skin and mucosal membranes causing histologically acanthosis and blisters and/or erosions[2]. Pemphigus is a potentially fatal condition; with the introduction of glucocorticoids (GC) in the 1950s, the mortality rate dramatically decreased from 75% to 30%4. GRs are encoded by the nuclear receptor subfamily 3, group C, member 1 (NR3C1) gene, which resides on chromosome 5q31–32, contains 10 exons, and codes for 777 amino acids[11]. This study aimed to evaluate the correlation between SNPs of the NR3C1 gene and GC resistance in PV patients

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Conclusion