Información del artículo
Estudios de asociación entre la densidad mineral ósea y los polimorfismos del gen del receptor de vitamina D arrojaron resultados muy contradictorios. Metaanálisis de dichos estudios indican que existe efecto de poca magnitud de los genotipos Bsm I sobre la densidad mineral ósea. Otros polimorfismos del gen del receptor de vitamina D, tales como el del sitio de restricción Fok I y el del sitio de unión de Cdx 2, tendrían efectos funcionales en la síntesis o la estabilidad de su ARNm, con consecuencias en la cantidad y/o la función del receptor de vitamina D. Es posible que los estudios de estos polimorfismos con los de otros genes candidatos y la interacción gen/medio ambiente arrojen más claridad. Los avances de la genética de la osteoporosis serían de utilidad no sólo para la identificación de individuos propensos a la enfermedad, sino también para el desarrollo de nuevos fármacos para la prevención y el tratamiento.
Palabras clave:
Osteoporosis
Receptor de vitamina D
Densidad mineral ósea
Masa ósea
Genotipos
Association studies of bone mineral density and polymorphisms of the vitamin D receptor gene have reported contradictory results. Meta-analyses of these studies indicate that certain Bsm I genotypes have a small effect on bone mineral density. Other polymorphisms of the vitamin D receptor gene, such as the restriction site Fok I and the binding site for Cdx2, have functional effects, either on vitamin D receptor mRNA synthesis or its stability, with final consequences on the quantity and/or function of vitamin D receptor protein. Studies of the interactions among these polymorphisms and others from different candidate genes, as well as of the interactions among gene/environmental factors, may lead to greater insight into this issue. Advances in the knowledge of the genetic basis of osteoporosis could be useful not only to identify individuals prone to developing osteoporosis, but also to design new drugs for the prevention and treatment of bone disease.
Key words:
Osteoporosis
Vitamin D receptor
Bone mineral density
Bone mass
Genotypes
El Texto completo está disponible en PDF
Bibliografía
[1.]
NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis and Therapy.
Osteoporosis prevention, diagnosis and therapy.
JAMA, 285 (2001), pp. 785-795
[2.]
L. Gennari, D. Merlotti, V. De Paola, A. Calabro, L. Becherini, G. Martini, et al.
Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review.
Am J Epidemiol, 161 (2005), pp. 307-320
[4.]
K.G. Faulkner, S.R. Cummings, D. Black, L. Palermo, C.C. Gluer, H.K. Genant.
Simple measurement of femoral geometry predicts hip fracture: The Study of Osteoporotic Fractures.
J Bone Miner Res, 8 (1993), pp. 1211-1217
[5.]
S.R. Cummings, M.C. Nevitt, W.S. Browner, K. Stone, K.M. Fox, K.E. Ensrud, et al.
Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group.
N Engl J Med, 332 (1995), pp. 767-773
[6.]
S. Ralston.
Genetic determinants of susceptibility to osteoporosis.
Curr Opin Pharmacol, 3 (2003), pp. 286-290
[7.]
E. Dennison, Z. Cole, C. Cooper.
Diagnosis and epidemiology of osteoporosis.
Curr Opin Rheumatol, 17 (2005), pp. 456-461
[8.]
S. Fujiwara.
Epidemiology of osteoporosis.
Clin Calcium, 15 (2005), pp. 577-582
[9.]
C.A. Mautalen.
Osteoporosis in Argentina.
Clin Calcium, 11 (2001), pp. 496-498
[10.]
T. O’Neill, D. Felsenberg, J. Varlow, C. Cooper, J. Kanis, A. Silman.
The prevalence of vertebral deformity in European men and women: the European Vertebral Osteoporosis Study.
J Bone Miner Res, 11 (1996), pp. 1010-1018
[11.]
A.G. Uitterlinden, Y. Fang, A.P. Bergink, J.B. Van Meurs, H.P. Van Leeuwen, H.A. Pols.
The role of vitamin D receptor gene polymorphisms in bone biology.
Mol Cell Endocrinol, 197 (2002), pp. 15-21
[12.]
F.E. McGuigan, G. Armbrecht, R. Smith, D. Felsenberg, D.M. Reid, S.H. Ralston.
Prediction of osteoporotic fractures by bone densitometry and COLIA1 genotyping: A prospective, population-based study in men and women.
Osteoporosis Int, 12 (2001), pp. 91-96
[13.]
N.A. Morrison, R. Yeoman, P.J. Kelly, J.A. Eisman.
Contribution of trans-acting factor alleles to normal physiological variability: Vitamin D receptor gene polymorphisms and circulating osteocalcin.
Proc Natl Acad Sci U S A, 89 (1992), pp. 6665-6669
[14.]
N.A. Morrison, J.C. Qi, A. Tokita, P.J. Kelly, L. Crofts, T.V. Nguyen, et al.
Prediction of bone mineral density from vitamin D receptor alleles.
Nature, 367 (1994), pp. 284-287
[15.]
N.A. Morrison, J.C. Qi, A. Tokita, P.J. Kelly, L. Crofts, T.V. Nguyen, et al.
Prediction of bone mineral density from vitamin D receptor alleles (correction).
Nature, 387 (1997), pp. 106
[16.]
G.S. Cooper, D.M. Umbach.
Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis.
J Bone Miner Res, 11 (1996), pp. 1841-1849
[17.]
G. Gong, H.S. Stern, S.C. Cheng, N. Fong, J. Mordeson, H.W. Deng, et al.
The association of bone mineral density with vitamin D receptor gene polymorphisms.
Osteoporosis Int, 9 (1999), pp. 55-64
[18.]
L.A. Rubin, G.A. Hawker, V.D. Peltekova, L.J. Fielding, R. Ridout, D.E.C. Cole.
Determinants of peak bone mass in a young female Canadian cohort.
J Bone Miner Res, 14 (1999), pp. 633-643
[19.]
S. Ferrari, R. Rizzoli, D. Slosman, J. Bonjour.
Do dietary calcium and age explain the controversy surrounding the relationship between bone mineral density and vitamin D receptor gene polymorphisms?.
J Bone Miner Res, 13 (1998), pp. 363-370
[20.]
A.G. Uitterlinden, A.E. Weel, H. Burger, Y. Fang, C.M. Van Dujin, A. Hofman, et al.
Interaction between the vitamin D receptor gene and collagen type 1a1 gene in susceptibility for fracture.
J Bone Miner Res, 16 (2001), pp. 379-385
[21.]
A. Thakkinstian, C. Déste, J. Eisman, T. Nguyen, J. Attia.
Meta-analysis of molecular association studies: Vitamin D receptor gene polymorphisms and BMD as a case study.
J Bone Miner Res, 19 (2004), pp. 419-428
[22.]
A. Thakkinstian, P. McElduff, C. Déste, D. Duffy, J. Attia.
A method for meta-analysis of molecular association studies.
Stat Med, 24 (2005), pp. 1291-1306
[23.]
S. Harris, T. Eccleshall, C. Gross, B. Dawson-Hughes, D. Feldman.
The vitamin D receptor start codon polymorphism (Fok I) and bone mineral density in premenopausal American black and white women.
J Bone Miner Res, 12 (1997), pp. 1043-1048
[24.]
H. Arai, K. Miyamoto, Y. Taketani, H. Yamamoto, Y. Iemori, K. Morita, et al.
A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women.
J Bone Miner Res, 12 (1997), pp. 915-921
[25.]
P.W. Jurutka, L.S. Remus, G.K. Whitfield, P.D. Thompson, J.C. Hsieh, E. Zitzer, et al.
The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factor IIB.
Mol Endocrinol, 14 (2000), pp. 401-420
[26.]
E.M. Colin, A.E. Weel, A.G. Uitterlinden, C.J. Burman, J.C. Birkenhager, H.A. Pols, et al.
Consequences of vitamin D receptor gene polymorphisms for growth inhibition of cultured human peripheral blood mononuclear cells by 1,25-dihydroxyvitamin D3.
Clin Endocrinol, 52 (2000), pp. 211-216
[27.]
H. Arai, K.I. Miyamoto, M. Yoshida, H. Yamamoto, Y. Taketani, K. Morita, et al.
The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene.
J Bone Miner Res, 16 (2001), pp. 1256-1264
[28.]
Y. Fang, J.B. Van Meurs, A.P. Bergink, A. Hofman, C.M. Van Dujin, J.P. Van Leeuwen, et al.
Cdx-2 polymorphisms in the promotor region of the human vitamin D receptor gene determine susceptibility to fracture in the elderly.
J Bone Miner Res, 18 (2003), pp. 1632-1641
[29.]
Y. Liu, Y. Liu, R. Recker, H. Geng.
Molecular studies of identification of genes for osteoporosis: the 2002 update.
J Endocrinol, 177 (2003), pp. 147-196
[30.]
A. Uitterlinden, Y. Fang, J. Van Meurs, H. Pols.
Genetic vitamin D receptor polymorphisms and risk of disease.
Vitamin D, pp. 1121-1157
[31.]
L. Raisz.
Pathogenesis of osteoporosis: concepts, conflicts and prospects.
J Clin Invest, 115 (2005), pp. 3318-3325
[32.]
M. Willing, M. Sowers, D. Aron, M. Clark, T. Burns, C. Bunten, et al.
Bone mineral density and its change in white women: estrogen and vitamin D receptor genotypes and their interaction.
J Bone Miner Res, 13 (1998), pp. 695-705
[33.]
E. Bandres, I. Pombo, M. González-Huarriz, A. Rebollo, G. López, J. García-Foncillas.
Association between bone mineral density and polymorphisms of the VDR, ER alpha, Col1A1 and CTR genes in Spanish postmenopausal women.
J Endocrinol Invest, 28 (2005), pp. 312-321
[34.]
M. Miyao, H. Morita, T. Hosoi, H. Kurihara, S. Inoue, S. Hoshino, et al.
Association of metylenetetrahydrofolate reductase (MTHFR) polymorphism with bone mineral density in postmenopausal Japanese women.
Calcif Tissue Int, 66 (2000), pp. 190-194
[35.]
N. Tolosa de Talamoni.
Genética de la osteoporosis.
Rev Arg Endocrinol, 39S (2002), pp. 33-34
[36.]
P. Garnero, O. Borel, E. Sornay-Rendu, P.D. Delmas.
Vitamin D receptor gene polymorphisms do not predict bone turnover and bone mass in healthy premenopausal women.
J Bone Miner Res, 10 (1995), pp. 1283-1288
[37.]
R. Lisker, M. López, S. Jasqui, S. Ponce de León Rosales, R. Correa-Rotter, S. Sanchez, et al.
Association of vitamin D receptor polymorphisms with osteoporosis in Mexican postmenopausal women.
Human Biol, 75 (2003), pp. 399-403
[38.]
N. Tolosa de Talamoni, A. Pérez, M. Ulla, V. Elias, E. Pretel, M. Mammana, et al.
Polymorphisms of vitamin D receptor and estrogen receptor genes in pre and perimenopausal women from the city of Córdoba, Argentina and surrounding areas: analysis of association with bone mineral density.
Bone, 37 (2005), pp. 127
[39.]
N. Tolosa de Talamoni, A. Pérez, L. Silvano, L. Muñoz, M. Binci, G. Sobrero, et al.
Polymorphisms of vitamin D receptor gene is associated to the phenotype and the bone mineral density in patients with Turner syndrome.
Bone, 36 (2005), pp. S249-S250
[40.]
N. Morrison.
Vitamin D receptor gene variants and osteoporosis: a contributor to the polygenic control of bone density.
Vitamin D, pp. 713-731
Copyright © 2007. Sociedad Española de Endocrinología y Nutrición
