Gene variants of glucocorticoid activation pathways and the outcomes of patients with Takayasu arteritis - a retrospective cohort study.

Objective: This study aims to evaluate the influence of polymorphisms of the HSD11B1, FKBP5 and NR3C1 genes on the outcomes of patients with Takayasu arteritis (TAK). Methods: A retrospective cohort study including 81 TAK patients was carried out. Polymorphisms of the genes HSD11B1 (rs11119328), FKBP5 (rs1360780) and NR3C1 (N363S, Bcll, TthIIII1, ER22/23EK and 9ß) were genotyped by the Sanger technique. Associations between the gene variants and the haplotypes (HT) of the NR3C1 gene with variables related to the outcome of TAK and glucocorticoid (GC)-related adverse events (AEs) were analyzed. Results: The polymorphism 9β of the NR3C1 gene, which leads to decreased GC sensitivity, was associated with a higher frequency of GC-related AEs [3.0 (2.0-3.8) vs. 2.0 (1.0-3.0); p = 0.002] and weight gain (37.5% vs. 8.9%; p = 0.012). Worsening glucose tolerance (i.e., a key GC-related AE) was an independent risk factor for acute ischemic events [odds ratio (OR) between 8.9 and 10.2] in all multivariate logistic regression models that included one of the polymorphisms in each model. Moreover, the carriage of 9β in the NR3C1 gene was also an independent risk factor for developing ischemic arterial events (OR: 4.4, 95% confidence interval: 1.1-18.3). None of the other polymorphisms of NR3C1, HSD11B1 and FKBP5 were associated with TAK features or outcomes, nor with GC-related AEs. Conclusion: Worsening glucose tolerance and the carriage of 9β of the NR3C1 gene were independent risk factors for acute ischemic events in TAK. The 9β polymorphism of the NR3C1 gene was associated with GC-related AEs in TAK in our patient population. None of the gene variants were predictors of sustained remission or arterial progression.