Single nucleotide polymorphism of RANKL and OPG genes may play a role in bone and joint injury in rheumatoid arthritis.

Objectives: This paper aims to investigate the influence of single-nucleotide polymorphisms (SNPs) in the receptor of activator of nuclear factor kappaB ligand (RANKL) gene (TNFSF11) and osteoprotegerin (OPG) gene (TNFRSF11B) on bone and joint injury in patients with rheumatoid arthritis (RA).

Methods: Two hundred RA patients and 201 matched controls were analysed by case-control design, and their samples were genotyped. Bone mineral density (BMD) and serum OPG and RANKL levels were measured. Clinical and laboratory parameters were recorded, and the radiographic changes in both hands of RA were evaluated by Sharp's method.

Results: Our results showed no significant differences in the distribution frequency of the alleles and genotypes of TNFRSF11B (rs2073618 and rs3102735) and TNFSF11 (rs2277438) between the RA group and controls (p>0.05). Compared to patients with TNFSF11 (rs2277438) AA or GG genotype, RA with TNFSF11 (rs2277438) AG genotype had significantly decreased BMD values at lumbar spine 3, lumbar spine 4, lumbar spine 2-4 (p<0.05-0.01), and apparently elevated Sharp scores (p<0.05), respectively. The RA group showed significantly higher serum levels of RANKL, RANKL/OPG ratio and a lower serum level of OPG than that of the controls (p<0.05-0.0001). RA patients with RANKL-rs2277438 heterozygotic genotype (AG) had significantly increased serum levels of RANKL (p<0.05), compared to homozygotic genotype (AA or GG).

Conclusions: These results indicate that SNP of TNFRSF11B (rs2073618 and rs3102735) and TNFSF11 (rs2277438) may not be susceptibility factors for RA in Chinese Han population. SNP of TNFSF11 (rs2277438) may have an important influence on bone and joint injury in RA.