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Transforming Growth Factor-β1 gene polymorphism and osteoporosis in postmenopausal egyptian women
Corresponding Author(s) : Azza M. Abdu Allah
Cellular and Molecular Biology,
Vol. 63 No. 11: Issue 11
Abstract
Transforming growth factor-β1 (TGF-β1) is a wide spread bone matrix protein that affect the function, formation and cell-cell interactions of osteoclasts and osteoblasts to regulate bone remodeling and sustain adequate bone mass. The aim of this study is to evaluate the role of the two polymorphism of transforming growth factor-β1 T869C and C-509T in developing osteoporosis in postmenopausal Egyptian women. This study was performed on 138 postmenopausal osteoporosis/osteopenic women and 128 postmenopausal female control group. There was a significant statistical difference in the CC, CT and TT (T869C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value <0.001). There was a non-significant statistical difference in the CC, CT and TT (T-509C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value <0.082). There was a significant statistical difference between TT,CT and CC of (T869C) and T score, Z score and calcium of osteopenia/osteoporosis group (p value <0.001). There was a non-significant statistical difference between TT, CT and CC of (T-509C) and T score, Z score of osteopenia/osteoporosis group (p value 0.32,0.31),but there was a statistically significant difference between the three genotyping and serum calcium and creatinine (p value 0.04). Multivariate regression analysis showed that T869C polymorphism is a significant risk factor for osteopenia/ osteoporosis (OR 3.57, 95% CI= 1.56-5.67). We concluded that T869C polymorphism of the TGF-β1 gene has an impact on bone mineral density and enhancement of the susceptibility to osteopenia/osteoporosis in Egyptian women.
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- -Zhao R. Immune regulation of bone loss by Th17 cells in oestrogen deficient osteoporosis. Eur J Clin Invest. 43:1195–1202. (2013).
- - Me´ndez JP, Rojano-Mejı´a D, Coral-Va´zquez RM, et al.,. Impact of genetic variants of IL-6, IL6R, LRP5 ESR1 and SP7 genes on bone mineral density in postmenopausal Mexican-Mestizo women with obesity. Gene. 528:216–220. (2013).
- -Aukasz A. Poniatowski, PiotrWojdasiewicz, Robert Gasik and DariuszSzukiewicz. Transforming Growth Factor Beta Family: Insight into the Role of Growth Factors in Regulation of Fracture HealingBiology and Potential Clinical Applications. Mediators of Inflammation, volume ; (2015).
- -WHO Scientific Group on the Prevention and Management of Osteoporosis . Geneva, (Switzerland) "Prevention and management of osteoporosis : report of a WHO scientific group" (pdf). (2003).Retrieved 2007-05-31
- - Simonet W. S., Lacey D. L., Dunstan C. R. et al.,. "Osteoprotegerin: a novel secreted protein involved in the regulation of bone density,” Cell, vol. 89, no. 2, pp. 309–319.(1997).
- - Hofbauer L. C., Khosla S., Dunstan C.R., Lacey D.L., Boyle W. J., and Riggs B. L.,."The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption,”Journal of Bone and Mineral Research, vol. 15, no. 1, pp. 2–12.(2000)
- - Bonewald L. F. and Mundy G. R.,. "Role of transforming growth factor-beta in bone remodeling,” Clinical Orthopaedics and Related Research, no. 250, pp. 261–276.(1990).
- - Shimpei Kasagi and Wanjun Chen . TGF-beta1 on osteoimmunology and the bone component cells. Cell & Bioscience .3:4.(2013).
- - Xi-Yu Wu, Yi-Qun Peng, Hong Zhang, Hui Xie, Zhi-Feng Sheng, Xiang-Hang Luo, Ru-Chun Dai, Hou-De Zhou, Xian-Ping Wu, and Er-Yuan Liao . Relationship between Serum Levels of OPG and TGF-ð”›½ with Decreasing Rate of BMD in Native Chinese Women. International Journal of Endocrinology. Article ID 727164, 8 pages. (2013).
- - Yoshiji Y . Association of a Leu10→Pro polymorphism of the transforming growth factor-beta1 with genetic susceptibility to osteoporosis and spinal osteoarthritis. Mech. Ageing Dev. 116: 113-123.(2000).
- - Jiajia Sun, MM, Chi Zhang, MM, Lei Xu, MM, Mingyuan Yang, MM, and Huilin Yang, MD. The Transforming Growth Factor-b1 (TGF-b1) GenePolymorphisms (TGF-b1 T869C and TGF-b1 T29C) and Susceptibility to Postmenopausal Osteoporosis A Meta-Analysis. Medicine, 94;(4). (2015).
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- - Yanagisawa J., Yanagi Y., Masuhiro Y. et al., . "Convergence of transforming growth factor-ð”›½ and vitamin D signaling pathways on SMAD transcriptional coactivators,” Science, vol. 283, no. 5406, pp. 1317–1321.(1999).
- Mori - S., Fuku N., Chiba Y. et al., . "Cooperative effect of serum 25-hydroxyvitamin D concentration and a polymorphism of transforming growth factor-ð”›½1 gene on the prevalence of vertebral fractures in postmenopausal osteoporosis,” Journal of Bone and Mineral Metabolism, vol. 28, no. 4, pp. 446–450.(2010).
- - Cohen MM Jr : TGF beta/Smad signaling system and its pathologic correlates. Am J Med Genet A. 116:1-10.(2003).
- -Peter Tzakas, Betty YL Wong, Alexander G Logan, Laurence A Rubinand David EC Cole. Transforming growth factor beta-1 (TGFB1) and peak bone mass: association between intragenic polymorphisms and quantitative ultrasound of the heel. BMC Musculoskeletal Disorders . 6:29.(2005).
- - Utennam D., Tungtrongchitr A., Phonrat B., Tungtrongchitr R., and Preutthipan S. Association of T869C gene polymorphism of transforming growth factor-ð”›½1 with low protein levels and anthropometric indices in osteopenia/osteoporosis postmenopausal Thai women, Genetics and Molecular Research,.Vol.11: (1), pp. 87–99. (2012).
- - Derynck R, Rhee L, Chen EY and Van Tilburg A . Intron-exon structure of the human transforming growth factor-b precursor gene. Nucleic Acids Res. 15: 3188-3189. (1987).
- - Yamada Y, Miyauchi A, Takagi Y, Tanaka M, et al.,. Association of the C-509→T polymorphism, alone or in combination with the T869→C polymorphism, of the transforming growth factor-β1 gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women. J. Mol. Med. 79: 149-156.(2001).
- - Hinke V, Seck T, Clanget C, Scheidt-Nave C, et al., . Association of transforming growth factor-beta1 (TGFbeta1) T29→C gene polymorphism with bone mineral density (BMD), changes in BMD, and serum concentrations of TGF-beta1 in a population-based sample of postmenopausal German women. Calcif. Tissue Int. 69: 315-320. (2001).
- - Lau HH, Ho AY, Luk KD, et al., . Transforming growth factor-beta1gene polymorphisms and bone turnover, bone mineral density and fracture risk in southern Chinese women. J Bone Miner Metab.;22:148–152.(2004).
- - Langdahl BL, Carstens M, Stenkjaer L and Eriksen EF . Polymorphisms in the transforming growth factor β 1 gene and osteoporosis. Bone 32: 297-310.(2003).
- - Tural S, Alayli G, Kara N, et al., .Association between osteoporosis and polymorphisms of the IL-10 and TGF-beta genes in Turkish postmenopausal women. Hum Immunol.;74:1179–1183.(2013).
- - McGuigan FE, Macdonald HM, Bassiti A, Farmer R, et al., . Large-scale population-based study shows no association between common polymorphisms of the TGFB1gene and BMD in women. J. Bone Miner. Res.22: 195-202. (2007)
References
-Zhao R. Immune regulation of bone loss by Th17 cells in oestrogen deficient osteoporosis. Eur J Clin Invest. 43:1195–1202. (2013).
- Me´ndez JP, Rojano-Mejı´a D, Coral-Va´zquez RM, et al.,. Impact of genetic variants of IL-6, IL6R, LRP5 ESR1 and SP7 genes on bone mineral density in postmenopausal Mexican-Mestizo women with obesity. Gene. 528:216–220. (2013).
-Aukasz A. Poniatowski, PiotrWojdasiewicz, Robert Gasik and DariuszSzukiewicz. Transforming Growth Factor Beta Family: Insight into the Role of Growth Factors in Regulation of Fracture HealingBiology and Potential Clinical Applications. Mediators of Inflammation, volume ; (2015).
-WHO Scientific Group on the Prevention and Management of Osteoporosis . Geneva, (Switzerland) "Prevention and management of osteoporosis : report of a WHO scientific group" (pdf). (2003).Retrieved 2007-05-31
- Simonet W. S., Lacey D. L., Dunstan C. R. et al.,. "Osteoprotegerin: a novel secreted protein involved in the regulation of bone density,” Cell, vol. 89, no. 2, pp. 309–319.(1997).
- Hofbauer L. C., Khosla S., Dunstan C.R., Lacey D.L., Boyle W. J., and Riggs B. L.,."The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption,”Journal of Bone and Mineral Research, vol. 15, no. 1, pp. 2–12.(2000)
- Bonewald L. F. and Mundy G. R.,. "Role of transforming growth factor-beta in bone remodeling,” Clinical Orthopaedics and Related Research, no. 250, pp. 261–276.(1990).
- Shimpei Kasagi and Wanjun Chen . TGF-beta1 on osteoimmunology and the bone component cells. Cell & Bioscience .3:4.(2013).
- Xi-Yu Wu, Yi-Qun Peng, Hong Zhang, Hui Xie, Zhi-Feng Sheng, Xiang-Hang Luo, Ru-Chun Dai, Hou-De Zhou, Xian-Ping Wu, and Er-Yuan Liao . Relationship between Serum Levels of OPG and TGF-ð”›½ with Decreasing Rate of BMD in Native Chinese Women. International Journal of Endocrinology. Article ID 727164, 8 pages. (2013).
- Yoshiji Y . Association of a Leu10→Pro polymorphism of the transforming growth factor-beta1 with genetic susceptibility to osteoporosis and spinal osteoarthritis. Mech. Ageing Dev. 116: 113-123.(2000).
- Jiajia Sun, MM, Chi Zhang, MM, Lei Xu, MM, Mingyuan Yang, MM, and Huilin Yang, MD. The Transforming Growth Factor-b1 (TGF-b1) GenePolymorphisms (TGF-b1 T869C and TGF-b1 T29C) and Susceptibility to Postmenopausal Osteoporosis A Meta-Analysis. Medicine, 94;(4). (2015).
- Hughes D. E., Dai A., J. C., Tiffee, H. H. Li, Munoy G. R., and Boyce B. F.,. "Estrogen promotes apoptosis ofmurine osteoclasts mediated by TGF-,” Nature Medicine, vol. 2, no. 10, pp. 1132–1135.(1996).
- Yanagisawa J., Yanagi Y., Masuhiro Y. et al., . "Convergence of transforming growth factor-ð”›½ and vitamin D signaling pathways on SMAD transcriptional coactivators,” Science, vol. 283, no. 5406, pp. 1317–1321.(1999).
Mori - S., Fuku N., Chiba Y. et al., . "Cooperative effect of serum 25-hydroxyvitamin D concentration and a polymorphism of transforming growth factor-ð”›½1 gene on the prevalence of vertebral fractures in postmenopausal osteoporosis,” Journal of Bone and Mineral Metabolism, vol. 28, no. 4, pp. 446–450.(2010).
- Cohen MM Jr : TGF beta/Smad signaling system and its pathologic correlates. Am J Med Genet A. 116:1-10.(2003).
-Peter Tzakas, Betty YL Wong, Alexander G Logan, Laurence A Rubinand David EC Cole. Transforming growth factor beta-1 (TGFB1) and peak bone mass: association between intragenic polymorphisms and quantitative ultrasound of the heel. BMC Musculoskeletal Disorders . 6:29.(2005).
- Utennam D., Tungtrongchitr A., Phonrat B., Tungtrongchitr R., and Preutthipan S. Association of T869C gene polymorphism of transforming growth factor-ð”›½1 with low protein levels and anthropometric indices in osteopenia/osteoporosis postmenopausal Thai women, Genetics and Molecular Research,.Vol.11: (1), pp. 87–99. (2012).
- Derynck R, Rhee L, Chen EY and Van Tilburg A . Intron-exon structure of the human transforming growth factor-b precursor gene. Nucleic Acids Res. 15: 3188-3189. (1987).
- Yamada Y, Miyauchi A, Takagi Y, Tanaka M, et al.,. Association of the C-509→T polymorphism, alone or in combination with the T869→C polymorphism, of the transforming growth factor-β1 gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women. J. Mol. Med. 79: 149-156.(2001).
- Hinke V, Seck T, Clanget C, Scheidt-Nave C, et al., . Association of transforming growth factor-beta1 (TGFbeta1) T29→C gene polymorphism with bone mineral density (BMD), changes in BMD, and serum concentrations of TGF-beta1 in a population-based sample of postmenopausal German women. Calcif. Tissue Int. 69: 315-320. (2001).
- Lau HH, Ho AY, Luk KD, et al., . Transforming growth factor-beta1gene polymorphisms and bone turnover, bone mineral density and fracture risk in southern Chinese women. J Bone Miner Metab.;22:148–152.(2004).
- Langdahl BL, Carstens M, Stenkjaer L and Eriksen EF . Polymorphisms in the transforming growth factor β 1 gene and osteoporosis. Bone 32: 297-310.(2003).
- Tural S, Alayli G, Kara N, et al., .Association between osteoporosis and polymorphisms of the IL-10 and TGF-beta genes in Turkish postmenopausal women. Hum Immunol.;74:1179–1183.(2013).
- McGuigan FE, Macdonald HM, Bassiti A, Farmer R, et al., . Large-scale population-based study shows no association between common polymorphisms of the TGFB1gene and BMD in women. J. Bone Miner. Res.22: 195-202. (2007)