-643C > T RANKL gene polymorphism is associated with osteoporosis in Tunisian postmenopausal women

Abstract

Objectives: The dynamic nature of the skeleton is achieved by a remodeling process. Receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) stimulates bone resorption by activating RANK signaling. Therefore it is considered as a candidate gene regulating susceptibility to osteoporosis. In the current study, we have investigated the association between the RANKL gene -693G > C and -643 C > T polymorphisms and bone mineral density (BMD) in a population of postmenopausal Tunisian women.

Methods: Polymorphic sites in RANKL gene (rs9533155 -693G > C and rs9533156 -643 C > T polymorphisms) were determined using PCR-RFLP analysis in 566 postmenopausal Tunisian women. All statistical analysis were examined by SPSS software.

Results: We have detected a significant difference in lumbar spine and hip BMD for -643C > T genotypes. For -693G > C genotypes, a significant difference was detected only in hip BMD. The distribution of -643C > T genotypes and alleles between three groups (osteoporotic, osteopenic and normal women) revealed a significant association of the TT genotype with development of osteoporosis (p = 0.01; odds ratio 2.15), although for the -693G > C polymorphism, no significant results were found.

Conclusion: We have demonstrated the association of the -643C > T polymorphism with BMD variation and osteoporosis risk in postmenopausal Tunisian women.

Keywords:

• RANKL
• -693G > C
• -643C > T
• lumbar spine BMD
• femoral neck BMD
• postmenopausal osteoporosis

Acknowledgements

The authors thank all the staff of the Genetics, Immunology and Human Pathologies Laboratory, Faculty of Mathematical, Physical and Natural Sciences of Tunis, Tunis EL Manar University, Tunisia and the staff of the Immuno-Rheumatology laboratory, Rabta Hospital, Faculty of Medicine of Tunis, Tunis EL Manar University, Tunisia for their skillful technical assistance. R.S. conceived and performed the molecular analysis and wrote the manuscript. H.S. was involved in clinical measurement. C.S. was involved in technical support and assistance. A.B.E.G. and S.S. designed the study. All authors read and approved the final manuscript.

Conflict of interest

We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Source of funding

This work was supported by the Tunisian Ministry of High Education, Research and Technology.