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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2009

Open Access 01-12-2009 | Research article

Variation in cytokine genes can contribute to severity of acetabular osteolysis and risk for revision in patients with ABG 1 total hip arthroplasty: a genetic association study

Authors: Jiri Gallo, Frantisek Mrazek, Martin Petrek

Published in: BMC Medical Genetics | Issue 1/2009

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Abstract

Background

The differences in total hip arthroplasty (THA) survivorship may be influenced by individual susceptibility to periprosthetic osteolysis. This may be driven by functional polymorphisms in the genes for cytokines and cytokine receptors involved in the development of osteolysis in THA, thereby having an effect on the individual's phenotype.

Methods

We performed a study on 22 single-nucleotide polymorphisms (SNPs) for 11 cytokines and two cytokine receptor candidate genes for association with severity of acetabular osteolysis and risk to failure in THA. Samples from 205 unrelated Caucasian patients with cementless type THA (ABG 1) were investigated. Distribution of investigated SNP variants between the groups of mild and severe acetabular osteolysis was determined by univariate and multivariate analysis. Time-dependent output variables were analyzed by the Cox hazards model.

Results

Univariate analysis showed: 1) TNF-238*A allele was associated with severe osteolysis (odds ratio, OR = 6.59, p = 0.005, population attributable risk, PAR 5.2%); 2) carriers of the IL6-174*G allele were 2.5 times more prone to develop severe osteolysis than non-carriers (OR = 2.51, p = 0.007, PAR = 31.5%); 3) the carriage of IL2-330*G allele was associated with protection from severe osteolysis (OR = 0.55, p = 0.043). Based on logistic regression, the alleles TNF-238*A and IL6-174*G were independent predictors for the development of severe acetabular osteolysis. Carriers of TNF-238*A had increased cumulative hazard of THA failure according to Cox model (p = 0.024). In contrast, IL2-330*G allele predicted lower cumulative hazard of THA failure (p = 0.019).

Conclusion

Genetic variants of proinflammatory cytokines TNF-alpha and IL-6 confer susceptibility to severe OL. In this way, presence of the minor TNF allele could increase the cumulative risk of THA failure. Conversely, SNP in the IL2 gene may protect carriers from the above THA complications.
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Literature
1.
Learmonth ID, Young C, Rorabeck C: The operation of the century: total hip replacement. Lancet. 2007, 370 (9597): 1508-1519. 10.1016/S0140-6736(07)60457-7.CrossRefPubMed
2.
Tuan RS, Lee FY, Y TK, Wilkinson JM, Smith RL: What are the local and systemic biologic reactions and mediators to wear debris, and what host factors determine or modulate the biologic response to wear particles?. J Am Acad Orthop Surg. 2008, 16 (Suppl 1): S42-48.CrossRefPubMedPubMedCentral
3.
Konttinen YT, Zhao D, Beklen A, Ma G, Takagi M, Kivela-Rajamaki M, Ashammakhi N, Santavirta S: The microenvironment around total hip replacement prostheses. Clin Orthop Relat Res. 2005, 28-38. 10.1097/01.blo.0000150451.50452.da. 430
4.
Vermes C, Chandrasekaran R, Jacobs JJ, Galante JO, Roebuck KA, Glant TT: The effects of particulate wear debris, cytokines, and growth factors on the functions of MG-63 osteoblasts. J Bone Joint Surg Am. 2001, 83-A (2): 201-211.PubMed
5.
Koulouvaris P, Ly K, Ivashkiv LB, Bostrom MP, Nestor BJ, Sculco TP, Purdue PE: Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis. J Orthop Res. 2008, 26 (1): 106-116. 10.1002/jor.20486.CrossRefPubMed
6.
Shanbhag AS, Kaufman AM, Hayata K, Rubash HE: Assessing osteolysis with use of high-throughput protein chips. J Bone Joint Surg Am. 2007, 89 (5): 1081-1089. 10.2106/JBJS.F.00330.CrossRefPubMed
7.
Sabokbar A, Itonaga I, Sun SG, Kudo O, Athanasou NA: Arthroplasty membrane-derived fibroblasts directly induce osteoclast formation and osteolysis in aseptic loosening. J Orthop Res. 2005, 23 (3): 511-519. 10.1016/j.orthres.2004.10.006.CrossRefPubMed
8.
Tunyogi-Csapo M, Kis-Toth K, Radacs M, Farkas B, Jacobs JJ, Finnegan A, Mikecz K, Glant TT: Cytokine-controlled RANKL and osteoprotegerin expression by human and mouse synovial fibroblasts: Fibroblast-mediated pathologic bone resorption. Arthritis Rheum. 2008, 58 (8): 2397-2408. 10.1002/art.23653.CrossRefPubMed
9.
Ramage SC, Urban NH, Jiranek WA, Maiti A, Beckman MJ: Expression of RANKL in osteolytic membranes: association with fibroblastic cell markers. J Bone Joint Surg Am. 2007, 89 (4): 841-848. 10.2106/JBJS.F.00655.CrossRefPubMed
10.
Wilkinson JM, Hamer AJ, Stockley I, Eastell R: Polyethylene wear rate and osteolysis: critical threshold versus continuous dose-response relationship. J Orthop Res. 2005, 23 (3): 520-525. 10.1016/j.orthres.2004.11.005.CrossRefPubMed
11.
Goodman SB: Wear particles, periprosthetic osteolysis and the immune system. Biomaterials. 2007, 28 (34): 5044-5048. 10.1016/j.biomaterials.2007.06.035.CrossRefPubMedPubMedCentral
12.
Granchi D, Cenni E, Trisolino G, Giunti A, Baldini N: Sensitivity to implant materials in patients undergoing total hip replacement. J Biomed Mater Res B Appl Biomater. 2006, 77 (2): 257-264.CrossRefPubMed
13.
Ollier WE: Cytokine genes and disease susceptibility. Cytokine. 2004, 28 (4-5): 174-178. 10.1016/j.cyto.2004.07.014.CrossRefPubMed
14.
Wilkinson JM, Wilson AG, Stockley I, Scott IR, Macdonald DA, Hamer AJ, Duff GW, Eastell R: Variation in the TNF gene promoter and risk of osteolysis after total hip arthroplasty. J Bone Miner Res. 2003, 18 (11): 1995-2001. 10.1359/jbmr.2003.18.11.1995.CrossRefPubMed
15.
Malik MH, Bayat A, Jury F, Kay PR, Ollier WE: Genetic susceptibility to total hip arthroplasty failure--positive association with mannose-binding lectin. J Arthroplasty. 2007, 22 (2): 265-270. 10.1016/j.arth.2006.02.163.CrossRefPubMed
16.
Malik MH, Jury F, Bayat A, Ollier WE, Kay PR: 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, 66 (8): 1116-1120. 10.1136/ard.2006.062018.CrossRefPubMedPubMedCentral
17.
Kolundzic R, Orlic D, Trkulja V, Pavelic K, Troselj KG: Single nucleotide polymorphisms in the interleukin-6 gene promoter, tumor necrosis factor-alpha gene promoter, and transforming growth factor-beta1 gene signal sequence as predictors of time to onset of aseptic loosening after total hip arthroplasty: preliminary study. J Orthop Sci. 2006, 11 (6): 592-600. 10.1007/s00776-006-1069-y.CrossRefPubMed
18.
Malik MH, Bayat A, Jury F, Ollier WE, Kay PR: Genetic susceptibility to hip arthroplasty failure--association with the RANK/OPG pathway. Int Orthop. 2006, 30 (3): 177-181. 10.1007/s00264-006-0074-2.CrossRefPubMedPubMedCentral
19.
Gordon A, Southam L, Loughlin J, Wilson AG, Stockley I, Hamer AJ, Eastell R, Wilkinson JM: Variation in the secreted frizzled-related protein-3 gene and risk of osteolysis and heterotopic ossification after total hip arthroplasty. J Orthop Res. 2007, 25 (12): 1665-1670. 10.1002/jor.20446.CrossRefPubMed
20.
Gordon A, Kiss-Toth E, Stockley I, Eastell R, Wilkinson JM: Polymorphisms in the interleukin-1 receptor antagonist and interleukin-6 genes affect risk of osteolysis in patients with total hip arthroplasty. Arthritis Rheum. 2008, 58 (10): 3157-3165. 10.1002/art.23863.CrossRefPubMed
21.
Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G, Hirschhorn JN, Abecasis G, Altshuler D, Bailey-Wilson JE, et al: Replicating genotype-phenotype associations. Nature. 2007, 447 (7145): 655-660. 10.1038/447655a.CrossRefPubMed
22.
Saleh KJ, Holtzman J, Gafni A, Saleh L, Davis A, Resig S, Gross AE: Reliability and intraoperative validity of preoperative assessment of standardized plain radiographs in predicting bone loss at revision hip surgery. J Bone Joint Surg Am. 2001, 83-A (7): 1040-1046.PubMed
23.
Gallo J, Langova K, Havranek V, Cechova I: Poor survival of ABG I hip prosthesis in younger patients. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2008, 152 (1): 163-168.CrossRefPubMed
24.
Engh CA, Massin P, Suthers KE: Roentgenographic assessment of the biologic fixation of porous-surfaced femoral components. Clin Orthop Relat Res. 1990, 107-128. 257
25.
Udomkiat P, Wan Z, Dorr LD: Comparison of preoperative radiographs and intraoperative findings of fixation of hemispheric porous-coated sockets. J Bone Joint Surg Am. 2001, 83-A (12): 1865-1870.PubMed
26.
Gallo J, Havranek V, Zapletalova J, Mandat D: Measurement of acetabular polyethylene wear of total hip replacement, using a universal measuring microscope. Characteristics of measurements. Acta Chir Orthop Traumatol Cech. 2006, 73 (1): 28-33. In CzechPubMed
27.
Gallo J, Havranek V, Cechova I, Zapletalova J: Wear measurement of retrieved polyethylene ABG 1 cups by universal-type measuring microscope and X-ray methods. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006, 150 (2): 321-326.CrossRefPubMed
28.
Javor J, Bucova M, Ferencik S, Grosse-Wilde H, Buc M: Single nucleotide polymorphisms of cytokine genes in the healthy Slovak population. Int J Immunogenet. 2007, 34 (4): 273-280. 10.1111/j.1744-313X.2007.00693.x.CrossRefPubMed
29.
Kubistova Z, Mrazek F, Tudos Z, Kriegova E, Ambruzova Z, Mytilineos J, Petrek M: Distribution of 22 cytokine gene polymorphisms in the healthy Czech population. Int J Immunogenet. 2006, 33 (4): 261-267. 10.1111/j.1744-313X.2006.00609.x.CrossRefPubMed
30.
Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988, 16 (3): 1215-10.1093/nar/16.3.1215.CrossRefPubMedPubMedCentral
31.
Hansen JA, (Ed): Immunobiology of the human MHC. Proceedings of the 13th International Histocompatibility Workshop and Conference. 2007, Seattle: IHWG Press, 1:
32.
Hutyrova B, Pantelidis P, Drabek J, Zurkova M, Kolek V, Lenhart K, Welsh KI, Du Bois RM, Petrek M: Interleukin-1 gene cluster polymorphisms in sarcoidosis and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2002, 165 (2): 148-151.CrossRefPubMed
33.
Mrazek F, Gallo J, Arakelyan A, Kubistova Z, Petrek M: Single nucleotide polymorphisms in genes for cytokines interleukin (IL)-2, IL-6 and TNFalpha influence severity of osteolysis after total hip arthroplasty. Tissue Antigens. 2008, 71 (4): 331-332.
34.
Wroblewski BM, Siney PD, Fleming PA: Charnley low-friction arthroplasty: survival patterns to 38 years. J Bone Joint Surg Br. 2007, 89 (8): 1015-1018. 10.1302/0301-620X.89B8.18387.CrossRefPubMed
35.
Kurreeman FA, Padyukov L, Marques RB, Schrodi SJ, Seddighzadeh M, Stoeken-Rijsbergen G, Helm-van Mil van der AH, Allaart CF, Verduyn W, Houwing-Duistermaat J, et al: A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. PLoS Med. 2007, 4 (9): e278-10.1371/journal.pmed.0040278.CrossRefPubMedPubMedCentral
36.
DeLee JG, Charnley J: Radiological demarcation of cemented sockets in total hip replacement. Clin Orthop Relat Res. 1976, 20-32. 121
37.
Little J, Higgins JP, Ioannidis JP, Moher D, Gagnon F, von Elm E, Khoury MJ, Cohen B, Davey-Smith G, Grimshaw J, et al: Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE Statement. Hum Genet. 2009, 125 (2): 131-151. 10.1007/s00439-008-0592-7.CrossRefPubMed
38.
Bayley JP, de Rooij H, Elsen van den PJ, Huizinga TW, Verweij CL: Functional analysis of linker-scan mutants spanning the -376, -308, -244, and -238 polymorphic sites of the TNF-alpha promoter. Cytokine. 2001, 14 (6): 316-323. 10.1006/cyto.2001.0902.CrossRefPubMed
39.
Sharma S, Ghosh B, Sharma SK: Association of TNF polymorphisms with sarcoidosis, its prognosis and tumour necrosis factor (TNF)-alpha levels in Asian Indians. Clin Exp Immunol. 2008, 151 (2): 251-259.CrossRefPubMedPubMedCentral
40.
Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P: The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998, 102 (7): 1369-1376. 10.1172/JCI2629.CrossRefPubMedPubMedCentral
41.
Terry CF, Loukaci V, Green FR: Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem. 2000, 275 (24): 18138-18144. 10.1074/jbc.M000379200.CrossRefPubMed
42.
Smith AJ, Humphries SE: Cytokine and cytokine receptor gene polymorphisms and their functionality. Cytokine Growth Factor Rev. 2009, 20 (1): 43-59. 10.1016/j.cytogfr.2008.11.006.CrossRefPubMed
43.
Schluter B, Raufhake C, Erren M, Schotte H, Kipp F, Rust S, Van Aken H, Assmann G, Berendes E: Effect of the interleukin-6 promoter polymorphism (-174 G/C) on the incidence and outcome of sepsis. Crit Care Med. 2002, 30 (1): 32-37. 10.1097/00003246-200201000-00005.CrossRefPubMed
44.
Michalek J, Svetlikova P, Fedora M, Klimovic M, Klapacova L, Bartosova D, Hrstkova H, Hubacek JA: Interleukin-6 gene variants and the risk of sepsis development in children. Hum Immunol. 2007, 68 (9): 756-760. 10.1016/j.humimm.2007.06.003.CrossRefPubMed
45.
Campos MI, Godoy dos Santos MC, Trevilatto PC, Scarel-Caminaga RM, Bezerra FJ, Line SR: Interleukin-2 and interleukin-6 gene promoter polymorphisms, and early failure of dental implants. Implant Dent. 2005, 14 (4): 391-396.CrossRefPubMed
46.
Zaiss MM, Axmann R, Zwerina J, Polzer K, Guckel E, Skapenko A, Schulze-Koops H, Horwood N, Cope A, Schett G: Treg cells suppress osteoclast formation: A new link between the immune system and bone. Arthritis Rheum. 2007, 56 (12): 4104-4112. 10.1002/art.23138.CrossRefPubMed
47.
Matesanz F, Fedetz M, Leyva L, Delgado C, Fernandez O, Alcina A: Effects of the multiple sclerosis associated -330 promoter polymorphism in IL2 allelic expression. J Neuroimmunol. 2004, 148 (1-2): 212-217. 10.1016/j.jneuroim.2003.12.001.CrossRefPubMed
48.
Hoffmann SC, Stanley EM, Darrin Cox E, Craighead N, DiMercurio BS, Koziol DE, Harlan DM, Kirk AD, Blair PJ: Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation. 2001, 72 (8): 1444-1450. 10.1097/00007890-200110270-00019.CrossRefPubMed
49.
Scola L, Candore G, Colonna-Romano G, Crivello A, Forte GI, Paolisso G, Franceschi C, Lio D, Caruso C: Study of the association with -330T/G IL-2 in a population of centenarians from centre and south Italy. Biogerontology. 2005, 6 (6): 425-429. 10.1007/s10522-005-4909-9.CrossRefPubMed
50.
Dupuis J, O'Donnell CJ: Interpreting results of large-scale genetic association studies: separating gold from fool's gold. JAMA. 2007, 297 (5): 529-531. 10.1001/jama.297.5.529.CrossRefPubMed
51.
52.
Chougle A, Hemmady MV, Hodgkinson JP: Severity of hip dysplasia and loosening of the socket in cemented total hip replacement. A long-term follow-up. J Bone Joint Surg Br. 2005, 87 (1): 16-20.PubMed
Metadata
Title
Variation in cytokine genes can contribute to severity of acetabular osteolysis and risk for revision in patients with ABG 1 total hip arthroplasty: a genetic association study
Authors
Jiri Gallo
Frantisek Mrazek
Martin Petrek
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2009
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-10-109

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