rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2008-653rsp-790Research ArticleСтатьиArticlesОценка значимости полиморфизмов генов LRP5,BVP4,TGFβl при постменопаузальном остеопорозеAssessment of genes LRP5, BVP4, TGF^l polymorphisms significance in postmenopausal osteoporosisMyakotkinKAMyakotkinKA-KrylovM. Y.KrylovM. Y.-KaseevaA. Y.KaseevaA. Y.-MaslovaK AMaslovaK A-ToroptsovaN. K.ToroptsovaN. K.-НикитинскаяО. А.NikitinskayaO A-BenevolenskayaL JBenevolenskayaL J-200815062008463№3 (2008)815Copyright © Myakotkin K., Krylov M.Y., Kaseeva A.Y., Maslova K.A., Toroptsova N.K., Никитинская О.А., Benevolenskaya L.J., 20082008Myakotkin K., Krylov M.Y., Kaseeva A.Y., Maslova K.A., Toroptsova N.K., Никитинская О.А., Benevolenskaya L.J.Myakotkin K., Krylov M.Y., Kaseeva A.Y., Maslova K.A., Toroptsova N.K., Nikitinskaya O.A., Benevolenskaya L.J.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/790

Резюме Выборку больных первичным постменопаузальным остеопорозом (ОП)составили 180 жен. (ср. возраст 67,5 + 7,8 лет) и 118 жен. в постменопаузе без ОП и остеопении в качестве контроля (ср. возраст 63,8 ± 8,1 лет). Выявлено увеличение частоты носительства генотипа СТ гена LRP5 (OR = 2,2; р = 0,005) и определенное накопление генотипа АА гена ВМР4 и генотипа СС гена TGFfi среди больных ОП по сравнению с контролем, однако различия статистически не значимы. Среди больных ОП отмечается накопление компаундов СТСС (комбинация генов LRP5и TGF\M) и CTAV (комбинация генов LRP5 и ВМР4), наличие которых повышает риск возникновения заболевания в 4 (р = 0,0004) и 2,5 (р = 0,035) раза соответственно. Показано наличие ассоциаций между LRP5 и TGFfil (г = 0,26 ; р = 0,001), между полиморфизмами этих генов и уровнем щелочной фосфатазы (г = 0,22; р = 0,004 и г = 0,16; р = 0, 04 соответственно) , между полиморфизмом гена ВМР4 и концентрацией осте- опротегерина в сыворотке крови (г = 0,2; р = 0,016). Выявлены ассоциации между комбинированными генотипами LRP5/TGF$1 и МПКТ шейки бедра (г = 0,20; р = 0, 014); LRP5/BMP4 и МПКТ трохантера (г = 0,16; р = 0,055). Более низкие средние значения МП К шейки бедра и трохантера отмечены у носителей генотипов СТ гена LRP5, ТТ гена TGF$1 и W гена ВМР4.

180 women with primary postmenopausal osteoporosis (OP) (mean age 67,5+7,8 years) were included. 118 postmenopausal women without osteoporosis and osteopenia (mean age 63,8±8,1 years) formed control group. Higher frequency of LRP5 gene CT genotype was revealed in pts with OP in comparison with control (OR=2,2; p=0,005). Tendency to increase of gene BMP4 AA genotype and gene TGFfi CC genotype was found in pts with OP in comparison with control. But the difference was not statistically significant. OP pts showed accumulation of CTCC (gene LRP5 and TGFfil combination) and CTAV (gene LRP5 and BMP4 combination) compounds increasing risk of the disease by a factor of 4 (p=0,0004) and 2,5 (p=0,035) respectively. Association was revealed between LRP5 and TGFfil (r=0,26; p=0,001), between polymorphisms of these genes and alkaline phosphatase level (r=0,22; p=0,004 and r=0,16; p=0,04 respectively), between gene BMP4 polymorphisms and serum osteoprotegerin concentration (r=0,2; p=0,0l6). Combined LRP5/TGF$1 genotype was associated with femur neck BMD (r=0,20; p=0,014) and LRP5/BMP4 - with trochanter BMD (r=0.16; p=0,055). Carriers of gene LRP5 CT genotype, gene TGFfil TT genotype and gene BMP4 W genotype had lower mean BMD values in femur neck and trochanter.

LRP5 — ген белка 5родственного белкам семейства рецептора липопротеинов низкой плотностиВМР4 — ген костного морфогенетического белка 4TGFfi 1 — ген трансформирующего фактора роста бета 1OPG — остеопротегеринRANKL — лиганд рецептора активатора ядерного фактора каппа ВКомпаунд — комбинация генотипов двух геновлокализованных на разных хромосомахReferences<div><p>Gong Y., Slee R.B., Fukai N. et al. LDL receptor- related protein 5 (LRP5) affects bone accrual and eye development. Cell, 2001, 107, 513-523.</p><p>Little R.D., Carulli J.P., Del Mastro R.G. et al. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am. J. Hum. Genet., 2002, 70, 11-19.</p><p>Krishan V., Bryant H.U., McDougald O.A. Regulation of bone mass by Wnt signaling. JCI, 2006, 116, 1202 - 1209.</p><p>Canalis E., Economides A., Gazzeito E. Bone Morphogenetic Proteins, Their Antagonists, and the Skeleton. Endocrine Reviews, 2003, 24, 218 — 235.</p><p>Janssens K., ten Dijke P., Janssens S., Wim Van Hul. Transforming Growth Factor — $1 to the bone. Endocrine Reviews, 2005, 26, 743-774.</p><p>Bezerra M.C., Carvalho J.F., Procopowitsch A.S., R. Pereira R.M. RANK, RANKL and osteoprotegerin in arthritic bone loss. Braz. J.Med.Biol.Res., 2005, 38, 161 - 170.</p><p>van Meurs J.B., Rivadeneira F., Jhamai M.et al. Common genetic variation of the low-density lipoprotein receptor-related protein 5 and 6 genes determines fracture risk in elderly white men. J. Bone Miner. Res., 2006, 21, 141-150.</p><p>Zofkova I., Hill M,.Zajickova K. Association of C/T Polymorphism^ in the LRP5 Gene with circulating follicle stimulating hormonein Caucasian postmenopausal women. Physiol.Res., 2007, 56, 735 - 739.</p><p>Zhang Z., Qin Y., Не I. et al. Association of polymorphisms in low density receptor—related protein 5 gene with bone mineral density in postmenopausal Chinese women. Acta Pharmocol. Sinisa, 2005, 26, 1111-1116.</p><p>Styrkarsdottir U., Cazier J.-B., Kong A. et at. Linkage of osteoporosis to chromosome 20p 12 and association to BMP2. PLoS Biol., 2003, 1. E69.</p><p>Ramesh B.L., Wilson S.G., Dick I. M.et al. Bone mass effects of a В MP4 gene polymorphism in postmenopausal women. Bone, 2005, 36, 555—561.</p><p>McGuidan F.A.E., Macdonald H.M., Bassiti A. et al. Large — scale population — based study shows no association between common polymorphisms of the TCRBI gene and BMD women. J.Miner.Res., 2007, 22, 195-202.</p><p>Langdahl B.L, Carstens М., Stenkjaer L., Eriksen. E.F. Polymorphisms in the transforming growth factor type 1 gene and osteoporosis. Bone, 2003, 32, 297 — 310.</p><p>Yamada Y., Miyauchi A., Takagi J. et al. Association of C—509—*T polymorphism, alone of in combination with the T869-C polymorphism, of the transforming growth factor — beta ! gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women. J. Mol. Med., 2001, 79, 149- 156.</p><p>Grainger D.J, Heathcote K, Chiano M. et al. Genetic control of the circulating concentration of transforming growth factor type 1. Hum.Mol.Genet., 1999, 8, 9397.</p></div><br /><div><p>Gong Y., Slee R.B., Fukai N. et al. LDL receptor- related protein 5 (LRP5) affects bone accrual and eye development. Cell, 2001, 107, 513-523.</p><p>Little R.D., Carulli J.P., Del Mastro R.G. et al. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am. J. Hum. Genet., 2002, 70, 11-19.</p><p>Krishan V., Bryant H.U., McDougald O.A. Regulation of bone mass by Wnt signaling. JCI, 2006, 116, 1202 - 1209.</p><p>Canalis E., Economides A., Gazzeito E. Bone Morphogenetic Proteins, Their Antagonists, and the Skeleton. Endocrine Reviews, 2003, 24, 218 — 235.</p><p>Janssens K., ten Dijke P., Janssens S., Wim Van Hul. Transforming Growth Factor — $1 to the bone. Endocrine Reviews, 2005, 26, 743-774.</p><p>Bezerra M.C., Carvalho J.F., Procopowitsch A.S., R. Pereira R.M. RANK, RANKL and osteoprotegerin in arthritic bone loss. Braz. J.Med.Biol.Res., 2005, 38, 161 - 170.</p><p>van Meurs J.B., Rivadeneira F., Jhamai M.et al. Common genetic variation of the low-density lipoprotein receptor-related protein 5 and 6 genes determines fracture risk in elderly white men. J. Bone Miner. Res., 2006, 21, 141-150.</p><p>Zofkova I., Hill M,.Zajickova K. Association of C/T Polymorphism^ in the LRP5 Gene with circulating follicle stimulating hormonein Caucasian postmenopausal women. Physiol.Res., 2007, 56, 735 - 739.</p><p>Zhang Z., Qin Y., Не I. et al. Association of polymorphisms in low density receptor—related protein 5 gene with bone mineral density in postmenopausal Chinese women. Acta Pharmocol. Sinisa, 2005, 26, 1111-1116.</p><p>Styrkarsdottir U., Cazier J.-B., Kong A. et at. Linkage of osteoporosis to chromosome 20p 12 and association to BMP2. PLoS Biol., 2003, 1. E69.</p><p>Ramesh B.L., Wilson S.G., Dick I. M.et al. Bone mass effects of a В MP4 gene polymorphism in postmenopausal women. Bone, 2005, 36, 555—561.</p><p>McGuidan F.A.E., Macdonald H.M., Bassiti A. et al. Large — scale population — based study shows no association between common polymorphisms of the TCRBI gene and BMD women. J.Miner.Res., 2007, 22, 195-202.</p><p>Langdahl B.L, Carstens М., Stenkjaer L., Eriksen. E.F. Polymorphisms in the transforming growth factor type 1 gene and osteoporosis. Bone, 2003, 32, 297 — 310.</p><p>Yamada Y., Miyauchi A., Takagi J. et al. Association of C—509—*T polymorphism, alone of in combination with the T869-C polymorphism, of the transforming growth factor — beta ! gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women. J. Mol. Med., 2001, 79, 149- 156.</p><p>Grainger D.J, Heathcote K, Chiano M. et al. Genetic control of the circulating concentration of transforming growth factor type 1. Hum.Mol.Genet., 1999, 8, 9397.</p></div><br />

The authors declare that there are no conflicts of interest present.