The Decisive Case-Control Study Elaborates the Null Association between ADAMTS5 rs226794 and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Case-Control Study
2.1.1. Ethical Issues
2.1.2. Subjects
2.1.3. Genomic DNA Extraction and Genotyping
2.1.4. Statistical Analysis
2.2. Meta-Analysis
2.2.1. Search Methods and Criteria for Study Consideration
2.2.2. Data Extraction
2.2.3. Statistical Analysis
3. Results
3.1. Case-Control Study
3.2. Meta-Analysis
3.3. TSA Evaluation
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Damen, J.; van Rijn, R.M.; Emans, P.J.; Hilberdink, W.K.H.A.; Wesseling, J.; Oei, E.H.G.; Bierma-Zeinstra, S.M.A. Prevalence and development of hip and knee osteoarthritis according to American College of Rheumatology criteria in the CHECK cohort. Arthritis Res Ther. 2019, 21, 4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Spector, T.D.; Cicuttini, F.; Baker, J.; Loughlin, J.; Hart, D. Genetic influences on osteoarthritis in women: A twin study. BMJ 1996, 312, 940–943. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Reginato, A.M.; Olsen, B.R. The role of structural genes in the pathogenesis of osteoarthritic disorders. Arthritis Res. 2002, 4, 337–345. [Google Scholar] [CrossRef] [PubMed]
- Takuwa, H.; Uchio, Y.; Ikegawa, S. Genome-wide association study of knee osteoarthritis: Present and future. Ann. Jt. 2018, 3, 64. [Google Scholar] [CrossRef]
- Glasson, S.S.; Askew, R.; Sheppard, B.; Carito, B.; Blanchet, T.; Ma, H.-L.; Flannery, C.R.; Peluso, D.; Kanki, K.; Yang, Z.; et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 2005, 434, 644–648. [Google Scholar] [PubMed]
- Malfait, A.M.; Liu, R.Q.; Ijiri, K.; Komiya, S.; Tortorella, M.D. Inhibition of ADAM-TS4 and ADAM-TS5 prevents aggrecan degradation in osteoarthritic cartilage. J. Biol. Chem. 2002, 277, 22201–22208. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rodriguez-Lopez, J.; Mustafa, Z.; Pombo-Suarez, M.; Malizos, K.N.; Rego, I.; Blanco, F.J.; Tsezou, A.; Loughlin, J.; Gomez-Reino, J.J.; Gonzalez, A. Genetic variation including nonsynonymous polymorphisms of a major aggrecanase, ADAMTS-5, in susceptibility to osteoarthritis. Arthritis Rheum. Off. J. Am. Coll. Rheumatol. 2008, 58, 435–441. [Google Scholar] [CrossRef] [PubMed]
- Canbek, U.; Imerci, A.; Kara, M.; Akgun, U.; Canbek, T.; Aydogan, N. Polymorphisms in ADAMTS4 and ADAMTS5 are not linked to susceptibility to knee osteoarthritis in the Turkish population. Genet Mol. Res. 2016, 15, 15038264. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.; Huang, C.; Cheng, Y.; Huang, J.; Wang, Q.; Liu, Q. Correlation study of disintegrin and metalloproteinase with thrombospondin motifs 5 gene single nucleotide polymorphism and osteoarthritis in Beijing. Chin. J. Rheumatol. 2015, 19, 512–517. [Google Scholar]
- Wu, N.; Chen, J.; Liu, H.; Zhao, L.; Liu, S.; Liu, J.; Su, X.; Wu, W.; Cong, J.; Qiu, G.; et al. The involvement of ADAMTS-5 genetic polymorphisms in predisposition and diffusion tensor imaging alterations of lumbar disc degeneration. J. Orthop. Res. 2014, 32, 686–694. [Google Scholar] [CrossRef] [PubMed]
- Gu, J.; Rong, J.; Guan, F.; Jiang, L.; Zhang, T.; Tao, S.; Guan, G.; Xu, L.; Tao, T. Association of ADAMTS5 gene polymorphisms with osteoarthritis in Chinese Han population: A community-based case—Control study. Rheumatol. Int. 2013, 33, 2893–2897. [Google Scholar] [CrossRef] [PubMed]
- Brok, J.; Thorlund, K.; Gluud, C.; Wetterslev, J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. J. Clin. Epidemiol. 2008, 61, 763–769. [Google Scholar] [CrossRef] [PubMed]
- Kellgren, J.H.; Lawrence, J.S. Radiological assessment of rheumatoid arthritis. Ann. Rheum. Dis. 1957, 16, 485–493. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009, 6, e1000097. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Viechtbauer, W. Conducting meta-analyses in R with the metafor package. J. Stat. Softw. 2010, 36, 1–48. [Google Scholar] [CrossRef] [Green Version]
- Schwarzer, G.; Carpenter, J.; Rücker, G. Meta-Analysis with R; Springer International Publishing: Cham, Switzerland, 2015. [Google Scholar]
- Thorlund, K.; Engstrøm, J.; Wetterslev, J.; Brok, J.; Imberger, G.; Gluud, C. False-Positive Findings in Cochrane Meta-Analyses with and without Application of Trial Sequential Analysis: An Empirical Review. Available online: https://bmjopen.bmj.com/content/6/8/e011890.short (accessed on 25 November 2021). [CrossRef]
- Zhou, X.; Jiang, L.; Zhang, Y.; Zhang, J.; Zhou, D.; Wu, L.; Huang, Y.; Xu, N. Genetic variation of aggrecanase-2 (ADAMTS5) in susceptibility to osteoarthritis. Braz. J. Med. Biol. Res. 2019, 52, e8109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huo, J.-Z.; Ji, X.-H.; Su, Z.-Y.; Shang, P.; Gao, F. Association of ADAMTS4 and ADAMTS5 polymorphisms with musculoskeletal degenerative diseases: A systematic review and meta-analysis. Biosci. Rep. 2018, 38, BSR20181619. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stanton, H.; Rogerson, F.M.; East, C.J.; Golub, S.B.; Lawlor, K.E.; Meeker, C.T.; Little, C.B.; Last, K.; Farmer, P.J.; Campbell, I.K.; et al. ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and In Vitro. Nature 2005, 434, 648–652. [Google Scholar] [CrossRef] [PubMed]
- Sterne, J.A.; Sutton, A.J.; Ioannidis, J.P.; Terrin, N.; Jones, D.R.; Lau, J.; Carpenter, J.; Rucker, G.; Harbord, R.M.; Schmid, C.H.; et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 2011, 343, d4002. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, C.; Chu, C.M.; Lin, J.; Yang, H.Y.; Su, S.L. Gene-gene and gene-environment interactions in meta-analysis of genetic association studies. PLoS ONE 2015, 10, e0124967. [Google Scholar] [CrossRef] [PubMed]
Knee OA Group (n = 606) | Control Group (n = 564) | p-Value | |
---|---|---|---|
Gender (%) | <0.001 * | ||
Male | 219 (36.1%) | 277 (49.1%) | |
Female | 387 (63.9%) | 287 (50.9%) | |
Age (mean±SD) | 73.45 ± 7.30 | 71.61 ± 6.79 | <0.001 * |
BMI | 24.58 ± 3.63 | 24.10 ± 3.31 | 0.021 * |
SBP (mmHg) | 133.39 ± 17.84 | 130.90 ± 16.96 | 0.016 * |
DBP (mmHg) | 77.13 ± 10.90 | 77.22 ± 11.09 | 0.882 |
KL Grade (%) | <0.001 * | ||
0 | 0 | 23 (4.1%) | |
1 | 0 | 541 (95.9%) | |
2 | 452 (74.6%) | 0 | |
3 | 83 (13.7%) | 0 | |
4 | 71 (11.7%) | 0 |
Knee OA Group (n = 606) | Control Group (n = 564) | Crude-OR (95% CI) | p-Value | Adj-OR a (95% CI) | p-Value | |
---|---|---|---|---|---|---|
Genotype | 0.667 | 0.785 | ||||
AA | 173 (28.5%) | 148 (26.2%) | 1.00 | 1.00 | ||
AG | 298 (49.2%) | 284 (50.4%) | 0.90 (0.68–1.18) | 0.438 | 0.91 (0.68–1.20) | 0.496 |
GG | 135(22.3%) | 132 (23.4%) | 0.87 (0.63–1.21) | 0.421 | 0.96 (0.68–1.35) | 0.805 |
Allele Model | 0.406 | 0.890 | ||||
A | 644 (53.1%) | 580 (51.4%) | 1.00 | 1.00 | ||
G | 568 (46.9%) | 548 (48.6%) | 0.93 (0.79–1.10) | 0.406 | 1.02 (0.76–1.36) | 0.890 |
Dominant Model | 0.377 | 0.551 | ||||
AA | 173 (28.5%) | 148 (26.2%) | 1.00 | 1.00 | ||
AG+ GG | 433 (71.5%) | 416 (73.8%) | 0.89 (0.69–1.15) | 0.377 | 0.92 (0.70–1.21) | 0.551 |
Recessive Model | 0.646 | 0.890 | ||||
AA+AG | 471 (77.7%) | 432 (76.6%) | 1.00 | 1.00 | ||
GG | 135 (22.3%) | 132 (23.4%) | 0.94 (0.71–1.23) | 0.646 | 1.02 (0.76–1.36) | 0.890 |
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Kao, C.-C.; Hsu, H.-E.; Chen, Y.-C.; Tu, M.-Y.; Chuang, S.-W.; Su, S.-L. The Decisive Case-Control Study Elaborates the Null Association between ADAMTS5 rs226794 and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis. Genes 2021, 12, 1916. https://doi.org/10.3390/genes12121916
Kao C-C, Hsu H-E, Chen Y-C, Tu M-Y, Chuang S-W, Su S-L. The Decisive Case-Control Study Elaborates the Null Association between ADAMTS5 rs226794 and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis. Genes. 2021; 12(12):1916. https://doi.org/10.3390/genes12121916
Chicago/Turabian StyleKao, Chung-Cheng, Hsiang-En Hsu, Yi-Chou Chen, Ming-Yu Tu, Su-Wen Chuang, and Sui-Lung Su. 2021. "The Decisive Case-Control Study Elaborates the Null Association between ADAMTS5 rs226794 and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis" Genes 12, no. 12: 1916. https://doi.org/10.3390/genes12121916