The role of osteoprotegerin (OPG) and estrogen receptor (ER-α) gene polymorphisms in rheumatoid arthritis.

Objective. Osteoclast activation at the cartilage pannus junction is an essential step in the destruction of bone matrix in patients affected by rheumatoid arthritis (RA). Receptor activator of NFkappaB ligand (RANK-L) is responsible for osteoclast differentiation and activation. Osteoprotegerin (OPG) is an alternative, high-affinity soluble receptor for RANK-L which significantly inhibits osteoclastogenesis. Estrogens and the specific receptors α and β (ER-α and ER-α) are known to play an important role in the pathophysiology of osteoarthritis (OA). Scope of the present study is to investigate the role of ER-α and OPG gene polymorphisms in a group of women affected by RA.Materials and Methods. 139 consecutive RA patients (115 females and 34 males; median age 65.8 years) were selected. Bone mineral density (BMD) was measured by dual energy x-ray absorptinometry at the lumbar spine (LS-BMD) and femoral neck (FN-BMD) and the presence of bone erosions was evaluated by conventional X-ray. ER-α gene polymorphisms were determined by PvuII and XbaI restriction endonuclease digestion of polymerase chain reaction (PCR) products. By convention, the presence of the endonuclease restriction site was indicated with lowercase (p and x) letters while the absence of the restriction site was indicated with uppercase letters (P and X). OPG gene polymorphism was determined by RsaI restriction endonuclease digestion of PCR products and the presence and absence of restriction fragment was identified as TT and CC respectively.Results. Pearson's χ(2)analysis for the ER-α gene polymorphism showed a prevalence of Pp genotype (58%) (p=0.04) and Xx (54%) (p=0.04) in the total population, without differences between males and females. We did not observed any significant differences between ER-α genotypes and LS-BMD. However subjects with xx or pp genotype had a lower LS-BMD in comparison with the opposite genotype.For OPG gene polymorphism, non significant differences in the distribution of the genotypes were observed between males and females. In addition, we did not observed significant differences on LS-BMD between the genotypes.Finally, we observed that patients with ER-α pp genotype was significant more represented in patients with hand erosions (p = 0.05). No significant correlation was observed for ER-α XbaI genotype, however a trend characterized by a correlation between xx and hand erosions was observed (p = 0.13). For OPG gene polymorphism, we found a statistical correlation between C allele of OPG and hands bone erosions (p = 0.02).Conclusion. We found a significant association between ER-α and OPG gene polymorphisms and the presence of bone erosions in RA patients. These preliminary data suggest a role of ER-α and OPG gene polymorphisms in bone turnover and disease progression.