NR3C1 Polymorphism and Steroid Responsiveness in CRSwNP: A Pharmacogenomic Study from South India

Abstract

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammatory condition of the nasal and sinus mucosa, often managed with corticosteroid therapy. However, patient responses to steroid treatment vary significantly, suggesting a potential role for pharmacogenomic factors. This study explores the pharmacogenomic variability influencing steroid responsiveness in patients with CRSwNP.Materials and Methods: This prospective observational study was conducted in the Department of Pharmacology, Annaii Medical College, Chennai, Tamil Nadu, India, from March 2012 to February 2013. A total of 92 patients diagnosed with CRSwNP and prescribed systemic corticosteroids were enrolled. Genetic polymorphisms in the NR3C1 (glucocorticoid receptor gene) and TBX21 (T-bet gene) were analyzed using PCR-RFLP techniques. Treatment response was evaluated using nasal symptom scores and endoscopic grading before and after a 4-week steroid regimen. Statistical analysis included Chi-square and independent t-tests, with p<0.05 considered significant.Results: Out of 92 patients, 58 (63.0%) were responders, and 34 (37.0%) were non-responders. The NR3C1 rs6198 polymorphism was significantly associated with treatment outcome (p = 0.014), with the GG genotype more prevalent in non-responders (47.1%). TBX21 rs2240017 showed no significant correlation (p = 0.417). Symptom score reduction was greater among those with the TT genotype (mean difference 2.6±0.8) than GG/GT (1.4±0.6).Conclusion: Genetic polymorphisms, particularly in the NR3C1 gene, appear to influence corticosteroid responsiveness in CRSwNP patients. Pharmacogenomic profiling may enhance personalized therapy and improve clinical outcomes.