Advances in Clinical and Experimental Medicine
2015, vol. 24, nr 2, March-April, p. 239–243
Publication type: original article
Toll-Like Receptor 4 Gene Polymorphism C1196T in Polish Women with Postmenopausal Osteoporosis – Preliminary Investigation
1 Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, Poland
2 Department of Biochemistry and Clinical Chemistry, Medical University of Warsaw, Poland
3 Department of Family Medicine, Internal Medicine and Metabolic Bone Diseases, Medical Center of Postgraduate Education, Professor Witold Orłowski Independent Public Clinical Hospital, Warszawa, Poland
Background. Postmenopausal osteoporosis is a systemic bone disease characterized by low bone mass after menopause. Bone remodeling is regulated by a number of factors, including the immune system. Toll-like receptors 4 (TLR4) are expressed on bone cells and modify the immune response. TLR4 gene polymorphism may take part in the development of chronic inflammation in women after menopause, which is the cause of severe bone resorption.
Objectives. To examine the frequency of TLR4 C1196T genotypes in postmenopausal osteoporotic and non-osteoporotic Polish women and to investigate the possible relationship between C1196T polymorphism, bone mineral density (BMD) and the incidence of osteoporotic fractures in this group of patients.
Material and Methods. The study involved 40 postmenopausal women with osteoporosis and 63 healthy postmenopausal non-osteoporotic women. BMD measurements were performed by dual-energy X-ray absorptiometry. DNA was extracted from peripheral blood. Genotyping was performed by real-time PCR using LightSNiP tests with SimpleProbe probes. Melting curve analysis of PCR amplicons enabled the identification of individual C1196T genotypes.
Results. C1196T genotype frequencies in the osteoporotic group were 88% for CC and 12% for CT. In the control group, respectively 86% and 14%. We did not observe the TT genotype. There was no association of C1196T genotypes and BMD nor the incidence of fractures but there was a correlation between genotypes and body height (p = 0.035, r = 0.415). Homozygous subjects for the C-allele had a lower body height with respect to heterozygous subjects.
Conclusion. It is unlikely that TLR4 C1196T polymorphism is related to bone mineral density and fracture incidence in Polish osteoporotic women after menopause. However, our data suggests that the C allele may be associated with lower body height in this group. Due to the small number of participants, our observations should be considered as preliminary. Larger studies are needed to confirm our findings.
polymorphism, gene, bone mineral density, postmenopausal osteoporosis, TLR4.
- Ralston SH, Uitterlinden AG: Genetics of osteoporosis. Endoc Rev 2010, 31, 629–662.
- Warriner AH, Saag KG: Osteoporosis diagnosis and medical treatment. Orthop Clin North Am 2013, 44, 125–135.
- Tatsuno I, Terano T, Nakamura M, Suzuki K, Kubota K, Yamaguchi J, Yoshida T, Suzuki S, Tanaka T, Shozu M: Lifestyle and osteoporosis in middle-aged and elderly women: Chiba bone survey. Endocr J 2013, 60, 643–650.
- Mundy GR: Osteoporosis and inflammation. Nutr Rev 2007, 65, 147–151.
- Zupan J, Jeras M, Marc J: Osteoimmunology and the influence of pro-inflammatory cytokines on osteoclasts. Biochem Med (Zagreb) 2013, 23, 43–63.
- Rauner M, Sipos W, Pietschmann P: Osteoimmunology. Int Arch Allergy Immunol 2007, 143, 31–48.
- Pacifici R: Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res 1996, 11, 1043–1051.
- Braun T, Schett G: Pathways for bone loss in inflammatory disease. Curr Osteoporos Rep 2012, 10, 101–108.
- Takeda K, Kaisho T, Akira S: Toll-like receptors. Annu Rev Immunol 2003, 21, 335–376.
- Barton GM, Medzhitov R: Toll-like receptor family members and their ligands. Curr Top Microbiol Immunol 2002, 270, 81–92.
- Nakashima T, Takayanagi H: Osteoimmunology: crosstalk between the immune and bone systems. J Clin Immunol 2009, 29, 555–567.
- Bandow K, Maeda A, Kakimoto K, Kusuyama J, Shamoto M, Ohnishi T, Matsuguchi T: Molecular mechanisms of the inhibitory effect of lipopolysaccharide (LPS) on osteoblast differentiation. Biochem Biophys Res Commun 2010, 402, 755–761.
- Bar-Shavit Z: Taking a toll on the bones: regulation of bone metabolism by innate immune regulators. Autoimmunity 2008, 41, 195–203.
- Walsh MC, Kim N, Kadono Y, Rho J, Lee SY, Lorenzo J, Choi Y: Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol 2006, 24, 33–63.
- Ferwerda B, McCall MB, Verheijen K, Kullberg BJ, van der Ven AJ, van der Meer JW, Netea MG: Functional consequences of toll-like receptor 4 polymorphisms. Mol Med 2008, 14, 346–352.
- Lorenzo J, Horowitz M, Choi Y: Osteoimmunology: interactions of the bone and immune system. Endocr Rev 2008, 29, 403–440.
- Mori G, D’Amelio P, Faccio R, Brunetti G: The interplay between the bone and the immune system. Clin Dev Immunol 2013, doi: 10.1155/2013/720504.
- Danks L, Takayanagi H: Immunology and bone. J Biochem 2013, 154, 29–39.
- Takayanagi H: New developments in osteoimmunology. Nat Rev Rheumatol 2012, 8, 684–689.
- Chen S: Association between the TLR4 + 896A > G (Asp299Gly) polymorphism and asthma: a systematic review and meta-analysis. J Asthma 2012, 49, 999–1003.
- Williams LK, Ownby DR, Maliarik MJ, Johnson CC: The role of endotoxin and its receptors in allergic disease. Ann Allergy Asthma Immunol 2009, 94, 323–332.
- Schröder NW, Schumann RR: Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lancet Infect Dis 2005, 5, 156–164.
- Zhang K, Zhou B, Wang Y, Rao L, Zhang L: The TLR4 gene polymorphisms and susceptibility to cancer: a systematic review and meta-analysis. Eur J Canc 2013, 49, 946–954.
- Richez C, Blanco P, Rifkin I, Moreau JF, Schaeverbeke T: Role for toll-like receptors in autoimmune disease: the example of systemic lupus erythematosus. Joint Bone Spine 2011, 78, 124–130.
- Cai H, Cai J, Tao G: Association of toll-like receptor 4 polymorphisms with type 2 diabetes mellitus. APMIS 2013, 121, 605–611.
- Noreen M, Shah MA, Mall SM, Choudhary S, Hussain T, Ahmed I, Jalil SF, Raza MI: TLR4 polymorphisms and disease susceptibility. Inflamm Res 2012, 61, 177–188.
- Johnson GB, Riggs BL, Platt JL: A genetic basis for the “Adonis” phenotype of low adiposity and strong bones. FASEB J 2004, 18, 1282–1284.
- Santos JL, Lera L, Pérez-Bravo F, Albala C: Adiposity and bone mineral density of Chilean elderly women in relation to toll-like receptor 4 gene polymorphisms. Ann Hum Biol 2006, 33, 585–592.
- Ozkan ZS, Deveci D, Yuce H: Investigation of association between TLR4 gene polymorphisms and osteoporosis in postmenauposal Turkish women. Int J Endocrinol Metab 2012, 10, 418–422.