Glucocorticoid Receptor Polymorphisms: Lack Of Association With Glucocorticoid Resistance In Chinese Bullous Disease Patients

Background: Bullous diseases are rare groups of autoimmune disease characterized by widespread blistering and erosions of skin and mucous membranes. Systemic glucocorticoids(GCs) are the cornerstone of management in severe bullous diseases, either for pemphigus or bullous pemphigoid. However, a considerable variability in the sensitivity to GCs across individuals and acquired GCs resistance have raised serious therapeutic concerns and limited the therapeutic response of patients. Recently Glucocorticoid receptor(GR) gene NR3C1 polymorphisms(rs41423247, rs6189/rs6190 and rs56149945) have been identified to determine GCs sensitivity in several autoimmune diseases. Objective: We investigated the associations between GR polymorphisms and GCs resistance in Chinese population with bullous diseases. Methods: we performed DNA sanger sequencing in 123 bullous patients(68pemphigus and 55 bullous pemphigoid) and 96 health controls in a Chinese Han population. Patients were divided into GCs-sensitivity(n=72, control dose≤40mg) and insensitivity groups(n=51, control dose≥150mg). After adjusting the age and gender, statistical analysis was performed using Chi-square test. Results: We analyzed the three SNPs of GR, rs6189/rs6190 and rs56149945 were confirmed as monomorphism, while only rs41423247 was confirmed as polymorphism. No significant association was identified between patients and controls as well as between sensitivity and insensitivity groups(P1=0.758, P2=0.522 respectively). We further analyzed the minor allele “G” frequency of rs41423247 in pemphigus and bullous pemphigoids groups, comparing to the healthy controls respectively. No significant associations were observed for both two disease subtype(P1=0.333, P2=0.075). In conclusion, no associations were found between rs41423247 polymorphism and GCs resistance, neither rs56149945 nor rs6189/rs6190 polymorphism was detected in Chinese patients with bullous diseases., which indicated the population heterogeneity. Conclusion: In summary, we confirmed Chinese population showed no association between polymorphisms of GR and glucocorticoids resistance with bullous diseases that suggested polymorphisms of GR influence glucocorticoids sensitivity may based on a different ethnic population. However more ethnic lines need to be researched to affirm the consideration and the cause of glucocorticoid resistance need further extensively studies.