The Role of Receptor Activator of Nuclear Factor Kappa B (RANK) and Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) in Osteoporosis Risk: Gene Polymorphism and Soluble RANKL Level in Indonesia Post-Menopausal Women

Abstract

Hormonal changes in postmenopausal women may increase osteoclastogenesis that can lead to increased risk of osteoporosis. Receptor Activator of Nuclear factor Kappa B (RANK) and Receptor Activator of Nuclear factor Kappa B Ligand (RANKL) have an important role in osteoclastogenesis that involve in the regulation of bone resorption. In this study, we analyzed the Single Nucleotide Polymorphism (SNPs) within the RANK/RANKL gene and the associated sRANKL level to assess the risk of osteoporosis in postmenopausal Indonesian women. Research was conducted as case control study that involved 210 postmenopausal Indonesian women. 105 of the women were classified as osteoporosis and 105 as normal. Genetic analysis was performed by PCR-RFLP. BMD was measured by Dual energy X-ray Absorptiometry (DXA) and the RANKL serum level was determined by ELISA. For statistical analysis, Chi-square testing, Kruskal Wallis testing, Mann-Whitney U testing and odds ratio testing were mainly applied, with a significance level of p<0.05. Genotype frequencies of RANK and RANKL polymorphism were compared between osteoporosis and normal group. Statistical analysis showed significant difference between the two group for genetic (p<0.05) and allele (p<0.05) of RANK gene (rs121908659) polymorphism. The elevated odd ratio suggests an increased risk (4.83-folds) to osteoporosis with the genotype CG in compare with genotype GG. No significant difference in RANK (rs1805034) and RANKL (rs9594759) in genotypes and allotypes. Even though there were no significant differences in the RANKL genotype, but we found that CT genotype was protective factor than CC genotypes. sRANKL levels in the RANKL genotype was significantly different (p<0.05), with RANKL level of TT genotype was higher than CC/CT genotype. Genotype and allele frequencies of RANK polymorphism (rs121908659) have been found to be associated with an elevated risk to osteoporosis in postmenopausal Indonesian women. Moreover, polymorphism of RANKL at the SNP location rs9594759 was significantly associated with level of sRANKL.