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Open Access 01-12-2017 | Research

Relationship between GNAS1 T393C polymorphism and aseptic loosening after total hip arthroplasty

Authors: Patrick Stelmach, Max D. Kauther, Lena Fuest, Gina Kurscheid, Thorsten Gehrke, Stefanie Klenke, Marcus Jäger, Christian Wedemeyer, Hagen S. Bachmann

Published in: European Journal of Medical Research | Issue 1/2017

Abstract

Background

Aseptic loosening is a main cause for revision surgery after total hip arthroplasty (THA) and there is no reliable marker for the early detection of patients at high risk. This study has been performed to validate association of the T393C polymorphism (rs7121) in the GNAS1 gene, encoding for the alpha-subunit of heterotrimeric G-protein Gs, with risk for and time to aseptic loosening after THA, which has been demonstrated in our previous study.

Methods

231 patients with primary THA and 234 patients suffering from aseptic loosening were genotyped for dependency on GNAS1 genotypes and analyzed.

Results

Genotyping revealed almost similar minor allele frequencies of 0.49 and 0.46, respectively. Consistently, genotype distributions of both groups were not significantly different (p = 0.572). Neither gender nor GNAS1 genotype showed a statistically significant association with time to loosening (p = 0.501 and p = 0.840). Stratification by gender, as performed in our previous study, was not able to show a significant genotype-dependent difference in time (female p = 0.313; male p = 0.584) as well as median time to aseptic loosening (female p = 0.353; male p = 0.868).

Conclusion

This study was not able to confirm the results of our preliminary study. An association of the GNAS1 T393C polymorphisms with risk for and time to aseptic loosening after THA is unlikely.

Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Jt Surg Am. 2007;89:780–5.

Dobzyniak M, Fehring TK, Odum S. Early failure in total hip arthroplasty. Clin Orthop Relat Res. 2006;447:76–8.CrossRefPubMed

Kurtz SM, Ong KL, Schmier J, Mowat F, Saleh K, Dybvik E, Karrholm J, Garellick G, Havelin LI, Furnes O, et al. Future clinical and economic impact of revision total hip and knee arthroplasty. J Bone Jt Surg Am. 2007;89(Suppl 3):144–51.

Wendelboe AM, Hegmann KT, Biggs JJ, Cox CM, Portmann AJ, Gildea JH, Gren LH, Lyon JL. Relationships between body mass indices and surgical replacements of knee and hip joints. Am J Prev Med. 2003;25:290–5.CrossRefPubMed

Flugsrud GB, Nordsletten L, Espehaug B, Havelin LI, Meyer HE. The effect of middle-age body weight and physical activity on the risk of early revision hip arthroplasty: a cohort study of 1,535 individuals. Acta Orthop. 2007;78:99–107.CrossRefPubMed

Dy CJ, Bozic KJ, Pan TJ, Wright TM, Padgett DE, Lyman S. Risk factors for early revision after total hip arthroplasty. Arthritis Care Res (Hoboken). 2014;66:907–15.CrossRef

Del Buono A, Denaro V, Maffulli N. Genetic susceptibility to aseptic loosening following total hip arthroplasty: a systematic review. Br Med Bull. 2012;101:39–55.CrossRefPubMed

Wedemeyer C, Kauther MD, Hanenkamp S, Nuckel H, Bau M, Siffert W, Bachmann HS. BCL2-938C>A and CALCA-1786T>C polymorphisms in aseptic loosened total hip arthroplasty. Eur J Med Res. 2009;14:250–5.CrossRefPubMedPubMedCentral

Puzhko S, Goodyer CG, Kerachian MA, Canaff L, Misra M, Juppner H, Bastepe M, Hendy GN. Parathyroid hormone signaling via Galphas is selectively inhibited by an NH(2)-terminally truncated Galphas: implications for pseudohypoparathyroidism. J Bone Miner Res. 2011;26:2473–85.CrossRefPubMedPubMedCentral

10.

Klenke S, Siffert W. SNPs in genes encoding G proteins in pharmacogenetics. Pharmacogenomics. 2011;12:633–54.CrossRefPubMed

11.

Patten JL, Johns DR, Valle D, Eil C, Gruppuso PA, Steele G, Smallwood PM, Levine MA. Mutation in the gene encoding the stimulatory G protein of adenylate cyclase in Albright’s hereditary osteodystrophy. N Engl J Med. 1990;322:1412–9.CrossRefPubMed

12.

Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune–Albright syndrome. N Engl J Med. 1991;325:1688–95.CrossRefPubMed

13.

Schwindinger WF, Francomano CA, Levine MA. Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune–Albright syndrome. Proc Natl Acad Sci USA. 1992;89:5152–6.CrossRefPubMedPubMedCentral

14.

Grigsby IF, Pham L, Gopalakrishnan R, Mansky LM, Mansky KC. Downregulation of Gnas, Got2 and Snord32a following tenofovir exposure of primary osteoclasts. Biochem Biophys Res Commun. 2010;391:1324–9.CrossRefPubMed

15.

Jia H, Hingorani AD, Sharma P, Hopper R, Dickerson C, Trutwein D, Lloyd DD, Brown MJ. Association of the G(s)alpha gene with essential hypertension and response to beta-blockade. Hypertension. 1999;34:8–14.CrossRefPubMed

16.

Bachmann HS, Lieb B, Bonnet U, Specka M, Augener S, Siffert W, Scherbaum N. Influence of the 393T>C polymorphism of the GNAS1 gene on the intensity of opiate withdrawal. Pharmacopsychiatry. 2011;44:159–60.CrossRefPubMed

17.

Lelonek M, Pietrucha T, Matyjaszczyk M, Goch JH. Mutation T/C, Ile 131 of the gene encoding the alfa subunit of the human Gs protein and predisposition to vasovagal syncope. Circ J. 2008;72:558–62.CrossRefPubMed

18.

Oterino A, Ruiz-Alegria C, Castillo J, Valle N, Bravo Y, Cayon A, Alonso A, Tejera P, Ruiz-Lavilla N, Munoz P, Pascual J. GNAS1 T393C polymorphism is associated with migraine. Cephalalgia. 2007;27:429–34.CrossRefPubMed

19.

Frey UH, Eisenhardt A, Lummen G, Rubben H, Jockel KH, Schmid KW, Siffert W. The T393C polymorphism of the G alpha s gene (GNAS1) is a novel prognostic marker in bladder cancer. Cancer Epidemiol Biomark Prev. 2005;14:871–7.CrossRef

20.

Frey UH, Lummen G, Jager T, Jockel KH, Schmid KW, Rubben H, Muller N, Siffert W, Eisenhardt A. The GNAS1 T393C polymorphism predicts survival in patients with clear cell renal cell carcinoma. Clin Cancer Res. 2006;12:759–63.CrossRefPubMed

21.

Frey UH, Alakus H, Wohlschlaeger J, Schmitz KJ, Winde G, van Calker HG, Jockel KH, Siffert W, Schmid KW. GNAS1 T393C polymorphism and survival in patients with sporadic colorectal cancer. Clin Cancer Res. 2005;11:5071–7.CrossRefPubMed

22.

Otterbach F, Callies R, Frey UH, Schmitz KJ, Wreczycki C, Kimmig R, Siffert W, Schmid KW. The T393C polymorphism in the gene GNAS1 of G protein is associated with survival of patients with invasive breast carcinoma. Breast Cancer Res Treat. 2007;105:311–7.CrossRefPubMed

23.

Minoretti P, Politi P, Coen E, Di Vito C, Bertona M, Bianchi M, Emanuele E. The T393C polymorphism of the GNAS1 gene is associated with deficit schizophrenia in an Italian population sample. Neurosci Lett. 2006;397:159–63.CrossRef

24.

El Hindy N, Lambertz N, Bachmann HS, Frey UH, Adamzik M, Zhu Y, Sure U, Siffert W, Sandalcioglu IE. Role of the GNAS1 T393C polymorphism in patients with glioblastoma multiforme. J Clin Neurosci. 2011;18:1495–9.CrossRefPubMed

25.

Zill P, Baghai TC, Zwanzger P, Schule C, Minov C, Behrens S, Rupprecht R, Moller HJ, Engel R, Bondy B. Association analysis of a polymorphism in the G-protein stimulatory alpha subunit in patients with major depression. Am J Med Genet. 2002;114:530–2.CrossRefPubMed

26.

Bachmann HS, Hanenkamp S, Kornacki B, Frey UH, Bau M, Siffert W, Wedemeyer C. Gender-dependent association of the GNAS1 T393C polymorphism with early aseptic loosening after total hip arthroplasty. J Orthop Res. 2008;26:1562–8.CrossRefPubMed

27.

Stelmach P, Wedemeyer C, Fuest L, Kurscheid G, Gehrke T, Klenke S, Jager M, Kauther MD, Bachmann HS. The BCL2-938C>A promoter polymorphism is associated with risk for and time to aseptic loosening of total hip arthroplasty. PLoS ONE. 2016;11:e0149528.CrossRefPubMedPubMedCentral

28.

Rodriguez S, Gaunt TR, Day IN. Hardy–Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol. 2009;169:505–14.CrossRefPubMedPubMedCentral

29.

Dupont WD, Plummer WD Jr. Power and sample size calculations for studies involving linear regression. Control Clin Trials. 1998;19:589–601.CrossRefPubMed

30.

Dupont WD, Plummer WD Jr. Power and sample size calculations. A review and computer program. Control Clin Trials. 1990;11:116–28.CrossRefPubMed

31.

Alakus H, Monig SP, Warnecke-Eberz U, Alakus G, Winde G, Drebber U, Schmitz KJ, Schmid KW, Riemann K, Siffert W, et al. Association of the GNAS1 T393C polymorphism with tumor stage and survival in gastric cancer. World J Gastroenterol. 2009;15:6061–7.CrossRefPubMedPubMedCentral

32.

Mahomed NN, Barrett JA, Katz JN, Phillips CB, Losina E, Lew RA, Guadagnoli E, Harris WH, Poss R, Baron JA. Rates and outcomes of primary and revision total hip replacement in the United States medicare population. J Bone Jt Surg Am. 2003;85-a:27–32.CrossRef

33.

Yan Y, Hu J, Lu H, Wang W. Genetic susceptibility to total hip arthroplasty failure: a case–control study on the influence of MMP 1 gene polymorphism. Diagn Pathol. 2014;9:177.CrossRefPubMedPubMedCentral

34.

Pan F, Hua S, Luo Y, Yin D, Ma Z. Genetic susceptibility of early aseptic loosening after total hip arthroplasty: the influence of TIMP-1 gene polymorphism on Chinese Han population. J Orthop Surg Res. 2014;9:108.CrossRefPubMedPubMedCentral

Title: Relationship between GNAS1 T393C polymorphism and aseptic loosening after total hip arthroplasty
Authors: Patrick Stelmach
Max D. Kauther
Lena Fuest
Gina Kurscheid
Thorsten Gehrke
Stefanie Klenke
Marcus Jäger
Christian Wedemeyer
Hagen S. Bachmann
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: European Journal of Medical Research / Issue 1/2017
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-017-0271-z

At a glance: The STEP trials

Springer Medicine

Relationship between GNAS1 T393C polymorphism and aseptic loosening after total hip arthroplasty

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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