Osteoprotegerin genetic polymorphisms and age of symptom onset in ankylosing spondylitis

Objectives: Osteoporosis is one of the recognized features of AS. It is known that RANK ligand (RANKL), which binds to RANK, can cause the activation of bone resorption. Osteoprotegerin (OPG) also competes with RANK by binding to RANKL and inhibiting bone absorption. Therefore, we designed a case-control study to evaluate the association between occurrence and clinical features of AS and RANK, RANKL and OPG genetic polymorphisms. Methods: A total of 330 AS patients and 330 age-and gender-matched controls were recruited. PCR-restriction fragment length polymorphism was applied to identify RANK C575T, RANKL C-290T and OPG G1181C genotypes. Results: OPG GG genotype carriers had an elevated risk of AS compared with those with the GC and CC genotypes (matched odds ratio 1.74; 95% CI 1.26, 2.40). Age of symptom onset and frequency of peripheral arthritis significantly differed among AS patients by OPG G1181C genotypes. HLA-B27+ patients with the OPG C allele had the earliest age of symptom onset [mean (S.D.) 26.6 (9.6) years], followed by HLA-B27+ patients with the OPG G allele [32.6 (12.2) years], HLA-B27- patients with the OPG G allele [38.1 (13.6) years] and HLA-B27- patients with the OPG C allele [38.6 (9.8) years]. Conclusion: OPG G1181C polymorphism may be associated with AS development and clinical manifestations.