Best Practice & Research Clinical Rheumatology
Volume 24, Issue 1 , Pages 3-14 , February 2010

The clinical relevance of genetic susceptibility to osteoarthritis

  • Ana M. Valdes, PhD (Senior Lecturer, Doctor)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +44 207 188 6765; Fax: +44 207 188 6718.
    • ,
  • Tim D. Spector, MD, FRCP (Professor, Doctor)

References 

  1. WHO . The burden of musculoskeletal conditions at the start of the new millennium. Geneva: WHO; 2003;
  2. Ding C, Cicuttini F, Jones G. How important is MRI for detecting early osteoarthritis?. Nat Clin Pract Rheumatol. 2008;4:4–5
  3. Goldring MB, Goldring SR. Osteoarthritis. J Cell Physiol. 2007 Dec;213(3):626–634
  4. Dieppe PA, Lohmander LS. Pathogenesis and management of pain in osteoarthritis. Lancet. 2005 Mar 12–18;365(9463):965–973
  5. Stecher RM. Heberden's nodes: heredity in hypertrophic arthritis of the finger joints. Am J Med Sci. 1941;210:801–809
  6. Risch N. Linkage strategies for genetically complex traits. Multilocus models. Am J Hum Genet. 1990;46:222–228
  7. Guo S-W. Sibling recurrence risk ratio as a measure of genetic effect: caveat emptor!. Am J Hum Genet. 2002;70(3):818–819
  8. Lanyon P, Muir K, Doherty S, et al. Assessment of a genetic contribution to osteoarthritis of the hip: sibling study. Br Med J. 2000;321(7270):1179–1183
  9. Neame RL, Muir K, Doherty S, et al. Genetic risk of knee osteoarthritis: a sibling study. Ann Rheum Dis. 2004;63(9):1022–1027
  10. Chitnavis J, Sinsheimer JS, Clipsham K, et al. Genetic influences in end-stage osteoarthritis. Sibling risks of hip and knee replacement for idiopathic osteoarthritis. J Bone Joint Surg Br. 1997;79:660–664
  11. Del Junco D, Luthra HS, Annegers JF, et al. The familial aggregation of rheumatoid arthritis and its relationship to the HLA-DR4 association. Am J Epidemiol. 1984;119(5):813–829
  12. Alarcon-Segovia D, Alarcon-Riquelme ME, Cardiel MH, et al. Familial aggregation of systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases in 1,177 lupus patients from the GLADEL cohort. Arthritis Rheum. 2005;52(4):1138–1147
  13. Moroldo MB, Chaudhari M, Shear E, et al. Juvenile rheumatoid arthritis affected sibpairs: extent of clinical phenotype concordance. Arthritis Rheum. 2004;50(6):1928–1934
  14. Weijnen CF, Rich SS, Meigs JB, et al. Risk of diabetes in siblings of index cases with Type 2 diabetes: implications for genetic studies. Diabet Med. 2002;19(1):41–50
  15. McDonnell SM, Sinsheimer J, Price AJ, et al. Genetic influences in the aetiology of anteromedial osteoarthritis of the knee. J Bone Joint Surg Br. 2007;89(7):901–903
  16. MacGregor AJ, Antoniades L, Matson M, et al. The genetic contribution to radiographic hip osteoarthritis in women: results of a classic twin study. Arthritis Rheum. 2000;43:2410–2416
  17. Lee YH, Rho YH, Choi SJ, et al. Osteoarthritis susceptibility loci defined by genome scan meta-analysis. Rheumatol Int. 2006;26(11):996–1000
  18. Valdes AM, Loughlin J, Oene MV, et al. Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee. Arthritis Rheum. 2007;56(1):137–146
  19. Min JL, Meulenbelt I, Riyazi N, et al. Association of the Frizzled-related protein gene with symptomatic osteoarthritis at multiple sites. Arthritis Rheum. 2005;52(4):1077–1080
  20. Valdes AM, Spector TD. The contribution of genes to osteoarthritis. Med Clin North Am. 2009 Jan;93(1):45–66
  21. Kizawa H, Kou I, Iida A, et al. An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis. Nat Genet. 2005;37(2):138–144
  22. Kaliakatsos M, Tzetis M, Kanavakis E, et al. Asporin and knee osteoarthritis in patients of Greek origin. Osteoarthritis Cartilage. 2006 Jun;14(6):609–611
  23. Rodriguez-Lopez J, Pombo-Suarez M, Liz M, et al. Lack of association of a variable number of aspartic acid residues in the asporin gene with osteoarthritis susceptibility: case-control studies in Spanish Caucasians. Arthritis Res Ther. 2006;8(3):R55
  24. Valdes AM, Hart DJ, Jones KA, et al. Association study of candidate genes for the prevalence and progression of knee osteoarthritis. Arthritis Rheum. 2004 Aug;50(8):2497–2507
  25. Valdes AM, Van Oene M, Hart DJ, et al. Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women. Arthritis Rheum. 2006;54(2):533–539
  26. Miyamoto Y, Mabuchi A, Shi D, et al. A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Genet. 2007 Apr;39(4):529–533
  27. Evangelou E, Chapman K, Meulenbelt I, et al. Large-scale analysis of association between GDF5 (rs143383) and FRZB (rs7775 and rs288326) variants and hip, knee and hand osteoarthritis. Arthritis Rheum; 60(6):1710–21.
  28. Valdes AM, Spector TD, Doherty S, et al. Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations. Ann Rheum Dis. 2008 Dec 3;[Epub ahead of print]
  29. Vaes RB, Rivadeneira F, Kerkhof JM, et al. Genetic variation in the GDF5 region is associated with osteoarthritis, height, hip axis length and fracture risk: the Rotterdam study. Ann Rheum Dis. 2008 Nov 24;[Epub ahead of print]
  30. Valdes AM, Loughlin J, van Meurs JB, et al. Genome-wide association scan identifies a prostaglandin-endoperoxide synthase 2 variant involved in risk of knee osteoarthritis. Am J Hum Genet. 2008 Jun;82(6):1231–1240
  31. Valdes AM, Hassett G, Hart DJ, et al. Radiographic progression of lumbar spine disc degeneration is influenced by variation at inflammatory genes: a candidate SNP association study in the Chingford cohort. Spine. 2005;30(21):2445–2451
  32. Smith AJ, Keen LJ, Billingham MJ, et al. Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. Genes Immun. 2004 Sep;5(6):451–460
  33. Meulenbelt I, Seymour AB, Nieuwland M, et al. Association of the interleukin-1 gene cluster with radiographic signs of osteoarthritis of the hip. Arthritis Rheum. 2004;50(4):1179–1186
  34. Kanoh T, Hasegawa Y, Masui T, et al. Interleukin-1 beta gene polymorphism associated with radiographic signs of osteoarthritis of the knee. J Orthop Sci. 2008 Mar;13(2):97–100
  35. Moxley G, Han J, Stern AG. Riley BP Potential influence of IL1B haplotype and IL1A-IL1B-IL1RN extended haplotype on hand osteoarthritis risk. Osteoarthritis Cartilage. 2007 Oct;15(10):1106–1112
  36. Pola E, Papaleo P, Pola R, et al. Interleukin-6 gene polymorphism and risk of osteoarthritis of the hip: a case-control study. Osteoarthritis Cartilage. 2005;13(11):1025–1028
  37. Nicklas BJ, Mychaleckyj J, Kritchevsky S, et al. Physical function and its response to exercise: associations with cytokine gene variation in older adults with knee osteoarthritis. J Gerontol A Biol Sci Med Sci. 2005;60(10):1292–1298
  38. Kämäräinen OP, Solovieva S, Vehmas T, et al. Common interleukin-6 promoter variants associate with the more severe forms of distal interphalangeal osteoarthritis. Arthritis Res Ther. 2008;10(1):R21
  39. Fytili P, Giannatou E, Karachalios T, et al. Interleukin-10G and interleukin-10R microsatellite polymorphisms and osteoarthritis of the knee. Clin Exp Rheumatol. 2005;23(5):621–627
  40. Riyazi N, Kurreeman FA, Huizinga TW, et al. The role of interleukin 10 promoter polymorphisms in the susceptibility of distal interphalangeal osteoarthritis. J Rheumatol. 2005;32(8):1571–1575
  41. Valdes AM, Lories RJ, van Meurs JB, et al. Variation at the ANP32A gene is associated with risk of hip osteoarthritis in women. Arthritis Rheum 60(7):2046–54.
  42. Meulenbelt I, Min JL, Bos S, et al. Identification of DIO2 as a new susceptibility locus for symptomatic osteoarthritis. Hum Mol Genet. 2008 Jun 15;17(12):1867–1875
  43. Lane NE, Lian K, Nevitt MC, et al. Frizzled-related protein variants are risk factors for hip osteoarthritis. Arthritis Rheum. 2006 Apr;54(4):1246–1254
  44. Smith AJ, Gidley J, Sandy JR, et al. Haplotypes of the low-density lipoprotein receptor-related protein 5 (LRP5) gene: are they a risk factor in osteoarthritis?. Osteoarthritis Cartilage. 2005;13(7):608–613
  45. van Meurs JB, Uitterlinden AG, Stolk L, et al. A functional polymorphism in the catechol-O-methyltransferase gene is associated with osteoarthritis-related pain. Arthritis Rheum. 2009 Feb;60(2):628–629
  46. Daans M, Lories RJ, Luyten FP. Dynamic activation of bone morphogenetic protein signaling in collagen-induced arthritis supports their role in joint homeostasis and disease. Arthritis Res Ther. 2008;10(5):R115
  47. Lane NE, Lin P, Christiansen L, et al. Association of mild acetabular dysplasia with an increased risk of incident hip osteoarthritis in elderly white women: the Study of Osteoporotic Fractures. Arthritis Rheum. 2000;43:400–404
  48. Doherty M, Courtney P, Doherty S, et al. Nonspherical femoral head shape (pistol grip deformity), neck shaft angle, and risk of hip osteoarthritis: A case-control study. Arthritis Rheum. 2008;58(10):3172–3182
  49. Sato MM, Nakashima A, Nashimoto M, et al. Bone morphogenetic protein-2 enhances Wnt/beta-catenin signaling-induced osteoprotegerin expression. Genes Cells. 2009 Feb;14(2):141–153
  50. Lodewyckx L, Lories RJ. WNT signaling in osteoarthritis and osteoporosis: what is the biological significance for the clinician?. Curr Rheumatol Rep. 2009 Feb;11(1):23–30
  51. Hartmann C, Tabin CJ. Dual roles of Wnt signaling during chondrogenesis in the chicken limb. Development. 2000 Jul;127(14):3141–3159
  52. Kerkhof JM, Uitterlinden AG, Valdes AM, et al. Radiographic osteoarthritis at three joint sites and FRZB, LRP5, and LRP6 polymorphisms in two population-based cohorts. Osteoarthritis Cartilage. 2008 Oct;16(10):1141–1149
  53. Li X, Cao X. BMP Signaling and Skeletogenesis. Ann NY Acad Sci. 2006;1068:26–40
  54. Rountree RB, Schoor M, Chen H, et al. BMP receptor signaling is required for postnatal maintenance of articular cartilage. PLoS Biol. 2004;2(11):e355
  55. Yang X, Chen L, Xu X, et al. TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage. J Cell Biol. 2001 Apr 2;153(1):35–46
  56. Rabier B, Williams AJ, Mallein-Gerin F, et al. Thyroid hormone-stimulated differentiation of primary rib chondrocytes in vitro requires thyroid hormone receptor beta. J Endocrinol. 2006 Oct;191(1):221–228
  57. Kim HA, Blanco FJ. Cell death and apoptosis in osteoarthritic cartilage. Curr Drug Targets. 2007 Feb;8(2):333–345
  58. Wei L, Sun XJ, Wang Z, Chen Q. CD95-induced osteoarthritic chondrocyte apoptosis and necrosis: dependency on p38 mitogen-activated protein kinase. Arthritis Res Ther. 2006;8(2):R37
  59. Rego-Pérez I, Fernández-Moreno M, Fernández-López C, et al. Mitochondrial DNA haplogroups: role in the prevalence and severity of knee osteoarthritis. Arthritis Rheum. 2008 Aug;58(8):2387–2396
  60. Rego I, Fernández-Moreno M, Fernández-López C, et al. The role of European mtDNA haplogroups in the prevalence of hip osteoarthritis in Galicia (Northern Spain). Ann Rheum Dis. 2009 Feb 17;[Epub ahead of print]
  61. Kidd BL, Photiou A, Inglis JJ. The role of inflammatory mediators on nociception and pain in arthritis. Novartis Found Symp. 2004;260:122–133discussion 133–8, 277–9
  62. Creamer P, Hunt M, Dieppe P. Pain mechanisms in osteoarthritis of the knee: effect of intra-articular anesthetic. J Rheumatol. 1996 Jun;23(6):1031–1036
  63. Benito MJ, Veale DJ, FitzGerald O, et al. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis. 2005;64(9):1263–1267
  64. Goldring MB, Berenbaum F. The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide. Clin Orthop Relat Res. 2004;427(Suppl.):S37–S46
  65. Ayral X, Pickering EH, Woodworth TG, et al. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis – results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthritis Cartilage. 2005 May;13(5):361–367
  66. Wörns MA, Victor A, Galle PR, et al. Genetic and environmental contributions to plasma C-reactive protein and interleukin-6 levels–a study in twins. Genes Immun. 2006;7(7):600–605
  67. Bonventre J. Cytosolic phospholipase A2alpha reigns supreme in arthritis and bone resorption. Trends Immunol. 2004 Mar;25(3):116–119
  68. Casas J, Gijón MA, Vigo AG, et al. Overexpression of cytosolic group IVA phospholipase A2 protects cells from Ca2+ -dependent death. J Biol Chem. 2006 Mar 3;281(9):6106–6116
  69. Szegedi A, Rujescu D, Tadic A, et al. The catechol-O-methyltransferase Val108/158Met polymorphism affects short-term treatment response to mirtazapine, but not to paroxetine in major depression. Pharmacogenomics J. 2005;5(1):49–53
  70. Nackley AG, Shabalina SA, Tchivileva IE, et al. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science. 2006 Dec 22;314(5807):1930–1933
  71. Mease PJ, Russell IJ, Kajdasz DK, et al. Long-term safety, tolerability, and efficacy of duloxetine in the treatment of fibromyalgia. Semin Arthritis Rheum. 2009 Jan 17;[Epub ahead of print]
  72. Abu-Amer Y, Darwech I, Clohisy JC. Aseptic loosening of total joint replacements: mechanisms underlying osteolysis and potential therapies. Arthritis Res Ther. 2007;9(Suppl. 1):S6
  73. Malik MH, Jury F, Bayat A, et al. Genetic susceptibility to total hip arthroplasty failure: a preliminary study on the influence of matrix metalloproteinase 1, interleukin 6 polymorphisms and vitamin D receptor. Ann Rheum Dis. 2007 Aug;66(8):1116–1120
  74. Gordon A, Kiss-Toth E, Stockley I, et al. Polymorphisms in the interleukin-1 receptor antagonist and interleukin-6 genes affect risk of osteolysis in patients with total hip arthroplasty. Arthritis Rheum. 2008 Oct;58(10):3157–3165
  75. Dixon T, Shaw M, Ebrahim S, Dieppe P. Trends in hip and knee joint replacement: socioeconomic inequalities and projections of need. Ann Rheum Dis. 2004;63:825–830
  76. Eisenberg M, Distefano JJ. TSH-based protocol, tablet instability, and absorption effects on L-T4 bioequivalence. Thyroid. 2009 Feb;19(2):103–110
  77. Valdes AM, Doherty M, Spector TD. The additive effect of individual genes in predicting risk of knee osteoarthritis. Ann Rheum Dis. 2008 Jan;67(1):124–127

PII: S1521-6942(09)00086-2

doi: 10.1016/j.berh.2009.08.005

Best Practice & Research Clinical Rheumatology
Volume 24, Issue 1 , Pages 3-14 , February 2010

Article Tools

* Image Usage & Resolution