Association of Receptor Activator of Nuclear Factor kappa B Ligand (RANKL) (rs9533155, rs9533156) Gene Polymorphism with its Circulatory Level and Bone Mineral Density in Postmenopausal Women with and without Osteoporosis

Introduction: The gene that codes for the receptor activator of nuclear factor kappa B ligand (RANKL) has been identified as a key regulator of osteoclastogenesis. It plays a key role in the remodeling of bones by affecting bone resorption. Objectives: The current study aims to evaluate the association pattern of single nucleotide polymorphism (SNP) of RANKL gene polymorphisms (rs9533155 (693C>G), rs9533156 (643T>C)) with its circulatory level and Bone Mineral Density (BMD) in North Indian postmenopausal women. Methods: In this study, 165 postmenopausal osteoporotic women were enrolled as patients (age 54.44 ± 6.00 years) and 165 postmenopausal non-osteoporotic women were enrolled as controls (age 54.47 ± 6.46 years). The BMD of all recruited subjects was determined, followed by genetic analysis by Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) method. RANKL levels were also measured using Enzyme-Linked Immunosorbent Assay. Result: The current study demonstrated that the subjects with the GG genotype of rs9533155 have significantly decreased average BMD at the lumbar spine and forearm and increased RANKL serum levels as compared to homozygous wild-type CC and heterozygous CG genotypes. Furthermore, subjects with the homozygous wild TT genotype of rs9533156 showed significantly lower BMD at the femoral neck and higher RANKL serum level as compared to homozygous mutant CC and heterozygous TC genotypes. No significant difference was found in the frequency distribution of genotypes and alleles of rs9533155 and rs9533156 among osteoporotic patients and controls. Conclusion: Our results suggest that RANKL polymorphism may be linked to BMD variation and osteoporosis development in north Indian postmenopausal women.