Cristian Herrera1, Miguel Marcos2, Cristina Carbonell3, José Antonio Mirón-Canelo4, Gerard Espinosa5, Ricard Cervera5, Antonio-Javier Chamorro6. 1. Department of Medicine, University of Salamanca, Salamanca, Spain; Department of Cardiology, Hospital General Universitario Gregorio Marañon, Instituto de Investigacion Sanitaria Gregorio Marañon (IiSGM), Madrid, Spain. 2. Department of Medicine, University of Salamanca, Salamanca, Spain; Department of Internal Medicine, University Hospital of Salamanca-SACYL, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain. Electronic address: mmarcos@usal.es. 3. Department of Internal Medicine, University Hospital of Salamanca-SACYL, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain. 4. Department of Epidemiology, University of Salamanca, Salamanca, Spain. 5. Department of Autoimmune Diseases, Institut Clínic de Medicina i Dermatología, Hospital Clínic, Barcelona, Catalonia, Spain. 6. Department of Medicine, University of Salamanca, Salamanca, Spain; Department of Internal Medicine, University Hospital of Salamanca-SACYL, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
Abstract
INTRODUCTION: The human glucocorticoid receptor gene (NR3C1) is considered to play a role in the differences and sensitivities of the glucocorticoid response in individuals with autoimmune diseases. The objective of this study was to examine by means of a systematic review previous findings regarding allelic variants of NR3C1 in relation to the risk of developing systemic autoimmune diseases. METHODS: Studies that analysed the genotype distribution of NR3C1 allelic variants among patients with systemic autoimmune diseases were retrieved. A meta-analysis was conducted with a random effects model. Odds ratios (ORs) and their confidence intervals (CIs) were calculated. In addition, sub-analysis by ethnicity, sensitivity analysis and tests for heterogeneity of the results were performed. RESULTS: Eleven studies met the inclusion criteria for meta-analysis. We found no evidence that the analysed NR3C1 polymorphisms, rs6198, rs56149945, and rs6189/rs6190, modulate the risk of developing a systemic autoimmune disease. Nonetheless, a protective role for the minor allele of rs41423247 was found among Caucasians (OR=0.78; 95% CI: 0.65, 0.92; P=0.004). A subgroup analysis according to underlying diseases revealed no significant association either for Behçet's disease or rheumatoid arthritis, while correlations between NR3C1 polymorphisms and disease activity or response to glucocorticoids could not be evaluated due to insufficient data. CONCLUSIONS: There is no clear evidence that the analysed NR3C1 allelic variants confer a risk for developing systemic autoimmune diseases although the minor G allele of rs41423247 may be protective among Caucasians.
INTRODUCTION: The humanglucocorticoid receptor gene (NR3C1) is considered to play a role in the differences and sensitivities of the glucocorticoid response in individuals with autoimmune diseases. The objective of this study was to examine by means of a systematic review previous findings regarding allelic variants of NR3C1 in relation to the risk of developing systemic autoimmune diseases. METHODS: Studies that analysed the genotype distribution of NR3C1 allelic variants among patients with systemic autoimmune diseases were retrieved. A meta-analysis was conducted with a random effects model. Odds ratios (ORs) and their confidence intervals (CIs) were calculated. In addition, sub-analysis by ethnicity, sensitivity analysis and tests for heterogeneity of the results were performed. RESULTS: Eleven studies met the inclusion criteria for meta-analysis. We found no evidence that the analysed NR3C1 polymorphisms, rs6198, rs56149945, and rs6189/rs6190, modulate the risk of developing a systemic autoimmune disease. Nonetheless, a protective role for the minor allele of rs41423247 was found among Caucasians (OR=0.78; 95% CI: 0.65, 0.92; P=0.004). A subgroup analysis according to underlying diseases revealed no significant association either for Behçet's disease or rheumatoid arthritis, while correlations between NR3C1 polymorphisms and disease activity or response to glucocorticoids could not be evaluated due to insufficient data. CONCLUSIONS: There is no clear evidence that the analysed NR3C1 allelic variants confer a risk for developing systemic autoimmune diseases although the minor G allele of rs41423247 may be protective among Caucasians.