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

Abstract

AbstractsGlucocorticoid (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.

Single-Nucleotide Nr3C1 Gene Polymorphisms Affect Glucocorticosteroid Treatment Efficacy In Patients With Pemphigus Vulgaris

“…None of the 15 PV patients exhibited the rs6189, rs6190, rs6195, or rs6198 SNPs associated with GC e cacy in patients with in ammatory bowel disease and rheumatoid arthritis [10], [11], [12], [15]; our sample size may have been too small. A Chinese study found signi cant relationships between rs17209237, rs11745958, rs33388, and rs7701443 and GC e cacy in PV patients [17]. We also identi ed these SNPs; the genotype and allele frequencies were similar to those in Chinese patients.…”

“…We found correlations between three SNPs (rs17209237, rs117458958, and rs6196) and the clinical response to GCs. rs17209237 and rs117458958, located in introns, were rst shown to correlate with GC e cacy in PV patients by Fang et al [17]. However, of the 17 SNPs for each position in LD (r 2 > 0.8) in the CHB and JPT populations, none was predicted to be functional; further research is needed.…”

“…We found that rs17209237 (AA) and rs11745958 (CC) were "protective" in terms of times to the 50 and 25% PDAI scores (days), GC dose required (mg/kg), time to tapering, and average daily GC dose (mg/kg/day). Fang et al [17] found correlations between rs33388 and rs7701443 and GC e cacy. Although we also identi ed these polymorphisms, we failed to detect any correlation with GC e cacy.…”

“…Based on published data, we chose 10 SNPs reported to affect GC e cacy in patients with various diseases: rs17209237, rs11745958, rs33388, rs7701443, rs41423247, rs6189, rs6190, rs6195, rs6196, and rs6198 [10], [11], [12], [13], [14], [15], [16], [17]. Whole blood samples from all patients were collected in tubes containing ethylenediamine tetra-acetic acid (EDTA) and sent to our Biotechnology Center for TaqMan SNP genotyping [18].…”

“…Earlier studies reported that several NR3C1 single nucleotide polymorphisms (SNPs) (rs6189, rs6190, rs6195, rs6196, rs6198, and rs41423247) might correlate with GC e cacy in patients with in ammatory bowel disease, rheumatoid arthritis, asthma, and idiopathic nephrotic syndrome [10], [11], [12], [13], [14], [15], [16]. For PV patients, Fang et al [17] were the rst to report associations between NR3C1 SNPs and GC e cacy; rs11745958 C/T and rs17209237 A/G may be associated with increased risks of GC resistance, but rs33388 A/T and rs7701443 A/G with decreased risks. However, it remains unclear how these SNPs affect GC dose requirements and Pemphigus Disease Activity Index (PDAI) scores, and whether these parameters vary environmentally, ethnically, or genetically.…”