Osteoarthritis as a genetic condition | Revista Española de Cirugía Ortopédica y Traumatología (English Edition)

Información del artículo

Abstract

Osteoarthritis is an example of a complex disease, which arises from the interaction of genetic and environmental factors. In this paper we review the different types of studies that can be conducted in order to analyze the contribution of genetic factors to the pathogenesis of complex diseases as well as the genes whose polymorphisms have been associated to the risk of developing osteoarthritis.

The significant benefits that surgery can offer patients with advanced-stage osteoarthritis beg the question of whether there genetic studies are really of any use. The answer is clearly in the affirmative. On the one hand, an awareness of the genetic factors involved in the onset and development of osteoarthritis may help identify and control subgroups of individuals who are at a higher risk at an early stage. Furthermore, identification of the genes involves could help discover new therapeutic targets that may lead to effectively halting the process, which is something we cannot do with our patients at present.

Keywords:

Osteoarthritis

Genetics

Association studies

Polymorphisms

Resumen

La artrosis es un ejemplo de enfermedad compleja, que se origina por la interacción de factores genéticos y ambientales. En este trabajo revisamos los diferentes tipos de estudios que permiten analizar la contribución de los factores genéticos a la patogenia de las enfermedades complejas y los genes cuyos polimorfismos se han relacionado con el riesgo de desarrollar artrosis.

Dado el importante beneficio que aporta la cirugía a los pacientes con artrosis avanzada, cabría plantearse si estos estudios genéticos tienen realmente alguna utilidad. La respuesta es claramente afirmativa. Por un lado, el conocimiento de los factores genéticos implicados en la aparición y el desarrollo de la artrosis puede permitir identificar y controlar subgrupos de individuos de mayor riesgo en fases precoces. Por otro lado, la identificación de los genes involucrados puede llevar a determinar nuevas dianas terapéuticas que permitan frenar de manera eficaz el desarrollo del proceso, algo que no podemos ofrecer a nuestros pacientes en la actualidad.

Palabras clave:

Artrosis

Genética

Estudios de asociación

Polimorfismos

El Texto completo está disponible en PDF

References

[1.]

M.A. Cimmino, M. Parodi.

Risk factors for osteoarthritis.

Semin Arthritis Rheum, 34 (2005), pp. 29-34

Medline

[2.]

J.B. Van Meurs, T.A. Trikalinos, S.H. Ralston, S. Balcells, M.L. Brandi, K. Brixen, et al.

Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis.

JAMA, 299 (2008), pp. 1277-1290

http://dx.doi.org/10.1001/jama.299.11.1277 | Medline

[3.]

A.M. Valdes, T.D. Spector.

The contribution of genes to osteoarthritis.

Rheum Dis Clin North Am, 34 (2008), pp. 581-603

http://dx.doi.org/10.1016/j.rdc.2008.04.008 | Medline

[4.]

J. Chitnavis, J.S. Sinsheimer, K. Clipsham, J. Loughlin, B. Sykes, P.D. Burge, et al.

Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee replacement for idiopathic osteoarthritis.

J Bone Joint Surg Br, 79 (1997), pp. 660-664

Medline

[5.]

T.D. Spector, A.J. MacGregor.

Risk factors for osteoarthritis: genetics.

Osteoarthr Cartil, 12 (2004), pp. S39-S44

Medline

[6.]

J.J. Ryder, K. Garrison, F. Song, L. Hooper, J. Skinner, Y. Loke, et al.

Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review.

Ann Rheum Dis, 67 (2008), pp. 584-591

http://dx.doi.org/10.1136/ard.2007.073874 | Medline

[7.]

F.S. Syed, S. Khosla.

Mechanisms of sex steroid effects on bone.

Biochem Biophys Res Commun, 328 (2005), pp. 688-696

http://dx.doi.org/10.1016/j.bbrc.2004.11.097 | Medline

[8.]

P. Richette, M. Corvol, T. Bardin.

Estrogens, cartilage, and osteoarthritis.

Joint Bone Spine, 70 (2003), pp. 257-262

Medline

[9.]

K. Lian, L. Lui, J.M. Zmuda, M.C. Nevitt, M.C. Hochberg, J.M. Lee, et al.

Estrogen receptor alpha genotype is associated with a reduced prevalence of radiographic hip osteoarthritis in elderly Caucasian women.

Osteoarthr Cartil, 15 (2007), pp. 972-978

http://dx.doi.org/10.1016/j.joca.2007.02.020 | Medline

[10.]

S.Y. Jin, S.J. Hong, H.I. Yang, S.D. Park, M.C. Yoo, H.J. Lee, et al.

Estrogen receptor-alpha gene haplotype is associated with primary knee osteoarthritis in Korean population.

Arthritis Res Ther, 6 (2004), pp. R415-R421

http://dx.doi.org/10.1186/ar1207 | Medline

[11.]

A.P. Bergink, J.B. Van Meurs, J. Loughlin, P.P. Arp, Y. Fang, A. Hofman, et al.

Estrogen receptor alpha gene haplotype is associated with radiographic osteoarthritis of the knee in elderly men and women.

Arthritis Rheum, 48 (2003), pp. 1913-1922

http://dx.doi.org/10.1002/art.11046 | Medline

[12.]

A.M. Valdes, M. Van Oene, D.J. Hart, G.L. Surdulescu, J. Loughlin, M. Doherty, et al.

Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women.

Arthritis Rheum, 54 (2006), pp. 533-539

http://dx.doi.org/10.1002/art.21621 | Medline

[13.]

J. Loughlin, J.S. Sinsheimer, Z. Mustafa, A.J. Carr, K. Clipsham, V.A. Bloomfield, et al.

Association analysis of the vitamin D receptor gene, the type I collagen gene COL1A1, and the estrogen receptor gene in idiopathic osteoarthritis.

J Rheumatol, 27 (2000), pp. 779-784

Medline

[14.]

R. Baron, G. Rawadi.

Wnt signaling and the regulation of bone mass.

Curr Osteoporos Rep, 5 (2007), pp. 73-80

Medline

[15.]

F. Dell’accio, C. De Bari, N.M. El Tawil, F. Barone, T.A. Mitsiadis, J. O’Dowd, et al.

Activation of WNT and BMP signaling in adult human articular cartilage following mechanical injury.

Arthritis Res Ther, 8 (2006), pp. R139

http://dx.doi.org/10.1186/ar2029 | Medline

[16.]

N.E. Lane, K. Lian, M.C. Nevitt, J.M. Zmuda, L. Lui, J. Li, et al.

Frizzled-related protein variants are risk factors for hip osteoarthritis.

Arthritis Rheum, 54 (2006), pp. 1246-1254

http://dx.doi.org/10.1002/art.21673 | Medline

[17.]

J. Rodriguez-Lopez, M. Pombo-Suarez, M. Liz, J.J. Gomez-Reino, A. Gonzalez.

Further evidence of the role of frizzled-related protein gene polymorphisms in osteoarthritis.

Ann Rheum Dis, 66 (2007), pp. 1052-1055

http://dx.doi.org/10.1136/ard.2006.065938 | Medline

[18.]

J. Loughlin, B. Dowling, K. Chapman, L. Marcelline, Z. Mustafa, L. Southam, et al.

Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females.

Proc Natl Acad Sci USA, 101 (2004), pp. 9757-9762

http://dx.doi.org/10.1073/pnas.0403456101 | Medline

[19.]

R.J. Lories, J. Peeters, A. Bakker, P. Tylzanowski, I. Derese, J. Schrooten, et al.

Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice.

Arthritis Rheum, 56 (2007), pp. 4095-4103

http://dx.doi.org/10.1002/art.23137 | Medline

[20.]

A. Gordon, L. Southam, J. Loughlin, A.G. Wilson, I. Stockley, A.J. Hamer, et al.

Variation in the secreted frizzled-related protein-3 gene and risk of osteolysis and heterotopic ossification after total hip arthroplasty.

J Orthop Res, 25 (2007), pp. 1665-1670

http://dx.doi.org/10.1002/jor.20446 | Medline

[21.]

S. Ikegawa.

New gene associations in osteoarthritis: what do they provide, and where are we going?.

Curr Opin Rheumatol, 19 (2007), pp. 429-434

http://dx.doi.org/10.1097/BOR.0b013e32825b079d | Medline

[22.]

A.M. Valdes, D.J. Hart, K.A. Jones, G. Surdulescu, P. Swarbrick, D.V. Doyle, et al.

Association study of candidate genes for the prevalence and progression of knee osteoarthritis.

Arthritis Rheum, 50 (2004), pp. 2497-2507

http://dx.doi.org/10.1002/art.20443 | Medline

[23.]

H. Mototani, A. Mabuchi, S. Saito, M. Fujioka, A. Iida, Y. Takatori, et al.

A functional single nucleotide polymorphism in the core promoter region of CALM1 is associated with hip osteoarthritis in Japanese.

Hum Mol Genet, 14 (2005), pp. 1009-1017

http://dx.doi.org/10.1093/hmg/ddi093 | Medline

[24.]

T.D. Spector, R.H. Reneland, S. Mah, A.M. Valdes, D.J. Hart, S. Kammerer, et al.

Association between a variation in LRCH1 and knee osteoarthritis: a genome-wide single-nucleotide polymorphism association study using DNA pooling.

Arthritis Rheum, 54 (2006), pp. 524-532

http://dx.doi.org/10.1002/art.21624 | Medline

[25.]

S. Snelling, J.S. Sinsheimer, A. Carr, J. Loughlin.

Genetic association analysis of LRCH1 as an osteoarthritis susceptibility locus.

Rheumatology (Oxford), 46 (2007), pp. 250-252

[26.]

A.M. Valdes, J. Loughlin, K.M. Timms, J.J. Van Meurs, L. Southam, S.G. Wilson, et al.

Genome-wide association scan identifies a prostaglandin-endoperoxide synthase 2 variant involved in risk of knee osteoarthritis.

Am J Hum Genet, 82 (2008), pp. 1231-1240

http://dx.doi.org/10.1016/j.ajhg.2008.04.006 | Medline

Indexada en:

Síguenos:

Indexada en:

Síguenos:

Suscríbase a la newsletter