Association between osteoprotegerin and RANKL single nucleotide polymorphisms and destructive rhinosinusitis in patients with granulomatosis with polyangiitis.

Background: Chronic invasive rhinosinusitis with facial bone damage is a common cause of functional and social impairment in granulomatosis with polyangiitis (GPA) patients. To the best of our knowledge, there is no clinical or laboratory biomarker to predict bone damage.

Methods: This case-control study included 90 patients with GPA and 270 health controls (HCs). Patients were categorized according to the presence of tomographic facial bone erosions. Frequency of RANKL and osteoprotegerin single nucleotide polymorphisms (SNPs), analyzed by real-time polymerase chain reaction, were compared between patients and HCs, and between patients with and without bone damage. Clinical, therapeutic, and laboratory data were analyzed.

Results: Facial bone erosion was observed in 55.5% of patients. No difference was found in the frequency of SNPs between patients with GPA and HCs. GPA patients were compared according to the presence or absence of bone damage, and a difference was found in the frequencies of osteoprotegerin G1181C (rs2073618) and RANKL A290G (rs2277438). A multivariate analysis showed that the CC genotype of osteoprotegerin 1181 was independently associated with bone erosion (OR = 3.95, CI95%=1.20-13.00, P = 0.02), as were the presence of the G allele in RANKL A290G (OR = 6.13, CI95%=1.95-19.26, P = 0.002) and higher disease duration (OR = 1.08, CI95%=1,01-1.15, P = 0.04).

Conclusion: SNPs in osteoprotegerin G1181C and RANKL A290G may play a role in the development of destructive rhinosinusitis in patients with GPA. Genetic assessment may be useful for identifying high-risk individuals. This observational study might work as a basis for further research to better understand this association and clinical trials using RANKL/osteoprotegerin as therapeutic targets.