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中华老年骨科与康复电子杂志 ›› 2023, Vol. 09 ›› Issue (01) : 51 -58. doi: 10.3877/cma.j.issn.2096-0263.2023.01.010

Meta分析

生长分化因子5 rs143383基因多态性与膝关节骨关节炎相关性的Meta分析
王月鹏, 徐云峰†()   
  1. 046000　长治医学院研究生处
    046000　长治云峰医院骨科
  • 收稿日期:2022-11-26 出版日期:2023-02-05
  • 通信作者: 徐云峰
  • 基金资助:
    长治市科技局基金项目(2022sy008)

Association between growth differentiation factor 5rs143383 gene polymorphism and knee osteoarthritis: a Meta-Analysis

Yuepeng Wang, Yunfeng Xu†()   

  1. Graduate School, Changzhi Medical College, Changzhi 046000, China
    Department of Orthopedics, Changzhi Yunfeng Hospital, Changzhi 046000, China
  • Received:2022-11-26 Published:2023-02-05
  • Corresponding author: Yunfeng Xu
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引用本文：

王月鹏, 徐云峰. 生长分化因子5 rs143383基因多态性与膝关节骨关节炎相关性的Meta分析[J]. 中华老年骨科与康复电子杂志, 2023, 09(01): 51-58.

Yuepeng Wang, Yunfeng Xu. Association between growth differentiation factor 5rs143383 gene polymorphism and knee osteoarthritis: a Meta-Analysis[J]. Chinese Journal of Geriatric Orthopaedics and Rehabilitation(Electronic Edition), 2023, 09(01): 51-58.

目的

探究生长分化因子5（GDF5）rs143383基因多态性与膝关节骨性关节炎发生的相关性。

方法

检索建库至2022年1月1日已经发表的关于GDF5 rs143383基因多态性与膝关节骨性关节炎之间相关性的文献，检索数据库包括PubMed、Embase、Web of Science、中国知网、万方和维普数据库等。依据检索策略检索，16篇文献（17项数据）符合纳入排除标准，从所需研究中提取数据后，确定优势比（OR）及其95%置信区间（CI）以评估。通过漏斗图评估发表偏差。

结果

GDF5（rs143383）基因多态性与膝关节骨性关节炎发生之间具有明显相关性。在总体的等位基因模型（T vs C：OR=1.20，95% CI：1.14，1.26，P<0.01）、共显基因模型（TT vs CC：OR=1.45，95% CI：1.30，1.62，P<0.01）和显性基因模型（TT+TC vs CC：OR=1.29，95%CI：1.17, 1.43，P<0.01），均提示GDF5基因多态性与膝关节骨性关节炎的发生有明显相关性。此外，我们还根据种族进行亚组分型，通过亚组分析在亚洲人群以及高加索人群的等位基因模型（亚洲人群：T vs C：OR=1.22，95% CI：1.13，1.30，P<0.01；高加索人群：T vs C：OR=1.18，95% CI：1.10，1.26，P<0.01）、共显基因模型（亚洲人群：TT vs CC：OR=1.58，95% CI：1.33，1.88，P<0.01；高加索人群：TT vs CC：OR=1.37，95% CI：1.19，1.59，P<0.01）和显性基因模型（亚洲人群：TT+TC vs CC：OR=1.40，95% CI：1.18，1.65，P<0.01；高加索人群：TT+TC vs CC：OR=1.24，95% CI：1.08，1.42，P<0.01）中均观察到了GDF5 rs143383基因多态性与膝关节骨性关节炎发生显著的关联，然而在非洲人群中无明显关联。

结论

GDF5 rs143383基因多态性与膝关节骨性关节炎发生具有显著联系，尤其在亚洲人群和高加索人群中具有相关性。

关键词: 生长分化因子5, rs143383, 基因多态性, 膝关节骨性关节炎, Meta分析
Objective

To explore the relationship between growth differentiation factor 5 (GDF5) rs143383 gene polymorphism and knee osteoarthritis (KOA).

Methods

The literatures about the relationship between GDF5 rs143383 gene polymorphism and knee osteoarthritis published from January 1, 2022 were searched, including PubMed, Embase, Web of Science, China knowledge net, Wanfang and VIP database. According to the retrieval strategy, 16 articles (17 items of data) met the inclusion exclusion criteria. After extracting the data from the required research, the odds ratio (OR) and its 95% confidence interval (CI) were determined for evaluation. The publication deviation was evaluated by funnel chart.

Results

We found that there was a significant correlation between GDF5 rs143383 gene polymorphism and knee osteoarthritis. In the overall allele model (T vs C: OR=1.29, 95% CI: 1.14, 1.26, P<0.01), the codominant gene model (TT vs CC: OR=1.45, 95% CI: 1.30, 1.62, P<0.01) and the dominant gene model (TT + TC vs CC: OR=1.29, 95% CI: 1.17, 1.43, P<0.0l), it is suggested that there is a significant correlation between GDF5 gene polymorphism and the occurrence of knee osteoarthritis. In addition, we also subtyped according to race, through subgroup analysis of allele models in Asian and Caucasian populations (Asian population: T vs C: OR=1.22, 95% CI: 1.13, 1.30, P<0.01, Caucasian population: T vs C: OR=1.18, 95% CI: 1.10, 1.26, P<0.01) and codominant gene model (Asian population: TT vs CC: OR=1.58, 95% CI: 1.33, 1.88, P<0.01, Caucasian population: TT vs CC: OR=1.37, 95% CI: 1.19, 1.59, P<0.01) and dominant gene model (Asian population: TT + TC vs CC: OR=1.40, 95% CI: 1.18, 1.65, P<0.01, Caucasian population: TT + TC vs CC: OR=1.24, 95% CI: 1.08, 1.42, P<0.01). Significant association between GDF5 rs143383 gene polymorphism and knee osteoarthritis was observed in Asian and Caucasian populations, but no significant association was found in African population.

Conclusion

There is a significant association between GDF5 rs143383 gene polymorphism and knee osteoarthritis, especially in Asian and Caucasian populations.

Key words: GDF5, rs143383, Gene polymorphism, Osteoarthritis of knee joint, Meta analysis
图1 文献筛选流程图
表1 纳入文献的基本特征
纳入研究 国家 种族 KOA/对照 男性/女性 KOA Control
TT TC CC TT TC CC
Miyamoto等[10]2007 日本 亚洲人群 718/861 NA/NA 444 243 31 473 330 58
Southam等[11]2007 西班牙和英国 高加索人 623/2018 1204/1437 243 304 76 763 935 320
Chapman等[2]2008 荷兰 高加索人 142/724 NA/NA 54 72 16 289 331 104
Tsezou等[13]2008 德国 高加索人 251/267 144/374 95 126 30 99 125 44
姚晨等[14]2008 中国 亚洲人群 313/485 275/523 197 97 19 244 193 48
Vaes等[15]2009 荷兰 高加索人 667/2097 1096/1668 276 298 93 752 1014 331
Valdes等[16]2009 英国(Chingford） 高加索人 259/509 NA/NA 126 98 35 181 244 84
Valdes等[16]2009 英国（Nottingham） 高加索人 735/646 NA/NA 337 313 85 238 329 79
Cao等[17]2010 韩国 亚洲人 276/298 213/361 150 115 11 159 113 26
Takahash等[18]2010 日本 亚洲人 933/1225 477/1681 566 313 54 684 461 80
Tawonsawatruk等[19]2011 泰国 亚洲人 90/103 21/172 38 41 11 33 47 23
Shin等[20]2012 韩国 亚洲人 725/1737 1035/1409 382 305 38 942 689 106
Elazeem等[21]2017 埃及 非洲人 50/50 18/82 20 16 14 12 25 13
Mishra等[22]2017 印度 亚洲人 500/500 429/571 199 226 75 131 272 97
Ozcan等[23]2017 土耳其 高加索人 94/279 NA/NA 37 43 14 74 153 52
Mohasseb等[24]2019 埃及 非洲人 47/40 18/69 14 23 10 16 13 11
Zhang等[25]2019 中国 亚洲人 288/397 314/371 124 105 59 206 159 32
表2 纳入研究的文献质量评价
纳入研究 选择（最多评分: 4星） 组间可比性（最多评分：2星） 暴露(最多评分：3星） 总共
Miyamoto等[10]2007 ☆☆☆ ☆ ☆☆ ☆☆☆☆☆☆
Southam等[11]2007 ☆☆☆☆ ☆ ☆☆ ☆☆☆☆☆☆☆
Chapman等[2]2008 ☆☆☆☆ ☆ ☆☆ ☆☆☆☆☆☆☆
Tsezou等[13]2008 ☆☆☆☆ ☆ ☆☆ ☆☆☆☆☆☆☆
姚晨等[14]2008 ☆☆☆☆ ☆☆ ☆☆ ☆☆☆☆☆☆☆☆
Vaes等[15]2009 ☆☆☆☆ ☆☆ ☆☆ ☆☆☆☆☆☆☆☆
Valdes等[16]2009 ☆☆☆☆ ☆ ☆☆ ☆☆☆☆☆☆☆
Valdes等[16]2009 ☆☆☆☆ ☆ ☆☆ ☆☆☆☆☆☆☆
Takahash等[18]2010 ☆☆☆☆ ☆ ☆☆ ☆☆☆☆☆☆☆
Tawonsawatruk等[19]2011 ☆☆☆☆ ☆ ☆☆ ☆☆☆☆☆☆☆
Shin等[20]2012 ☆☆☆☆ ☆☆ ☆☆ ☆☆☆☆☆☆☆☆
Elazeem等[21]2017 ☆☆☆☆ ☆☆ ☆☆ ☆☆☆☆☆☆☆☆
Mishra等[22]2017 ☆☆☆ ☆ ☆☆ ☆☆☆☆☆☆
Ozcan等[23]2017 ☆☆☆☆ ☆ ☆☆ ☆☆☆☆☆☆☆
Mohasseb等[24]2019 ☆☆☆☆ ☆☆ ☆☆ ☆☆☆☆☆☆☆☆
Zhang等[25]2019 ☆☆☆☆ ☆ ☆ ☆☆☆☆☆☆
图3 GDF5 rs143383基因多态性与KOA发生关系共显基因模型的森林图（TT vs CC）
图6 敏感性分析
表3 GDF-5 rs143383基因多态性和KOA的Meta分析结果
等位基因和基因型 OR 95% CI P 模型 I2
总体          
T vs C 1.20 1.14，1.26 <0.01 F 43
TT vs CC 1.45 1.30，1.62 <0.01 F 0
TC vs CC 1.17 1.05-1.30 <0.01 F 1
TT+TC vs CC 1.29 1.17，1.43 <0.01 F 0
TT vs TC+CC 1.28 1.14，1.45 <0.01 R 66
亚洲人          
T vs C 1.22 1.13，1.30 <0.01 R 68
TT vs CC 1.58 1.33，1.88 <0.01 F 32
TC vs CC 1.23 1.03，1.46 <0.01 F 0
TT+TC vs CC 1.40 1.18，1.65 <0.01 F 0
TT vs TC+CC 1.31 1.08，1.59 <0.01 R 76
高加索人          
T vs C 1.18 1.10，1.26 <0.01 F 1
TT vs CC 1.37 1.19，1.59 <0.01 F 0
TC vs CC 1.13 0.98，1.31 0.09 F 3
TT+TC vs CC 1.24 1.08，1.42 <0.01 F 0
TT vs TC+CC 1.26 1.08，1.49 <0.01 R 60
非洲人          
T vs C 1.12 0.75，1.68 0.58 F 0
TT vs CC 1.24 0.58，2.65 0.54 F 0
TC vs CC 1.01 0.49，2.07 0.11 R 60
TT+TC vs CC 1.10 0.57，2.12 0.51 F 0
TT vs TC+CC 1.17 0.36，3.77 0.06 R 72
1
Vassão PG, Parisi JL, Penha TFC, et al. Association of photobiomodulation therapy (PBMT) and exercises programs in pain and functional capacity of patients with knee osteoarthritis (KOA): a systematic review of randomized trials [J]. Lasers Med Sci, 2021, 36(7): 1341-1353.
2
Khan S, Logan PC, Asokan A, et al. The assessment and management of the arthritic knee: an update [J]. Cureus, 2020, 12(11): e11582.
3
Salaffi F, Di Carlo M, Carotti M, et al. Frailty prevalence according to the Survey of Health, Ageing and Retirement in Europe-Frailty Instrument (SHARE-FI) definition, and its variables associated, in patients with symptomatic knee osteoarthritis: findings from a cross-sectional study [J]. Aging Clin Exp Res, 2021, 33(6): 1519-1527.
4
Sun X, Zhen X, Hu X, et al. Osteoarthritis in the Middle-Aged and Elderly in China: Prevalence and Influencing Factors. Int J Environ Res Public Health [J]. 2019, 16(23): 4701.
5
Tang X, Wang SF, Zhan SY, et al. The prevalence of symptomatic knee osteoarthritis in China: results from the China health and retirement longitudinal study [J]. Arthritis Rheumatol, 2016, 68(3): 648-653.
6
Charlesworth J, Fitzpatrick J, Perera NKP, et al. Osteoarthritis- a systematic review of long-term safety implications for osteoarthritis of the knee [J]. BMC Musculoskelet Disord, 2019, 20(1): 151.
7
Liu CY, Li CD, Wang L, et al. Function scores of different surgeries in the treatment of knee osteoarthritis: A PRISMA-compliant systematic review and network-meta analysis [J]. Medicine (Baltimore), 2018, 97(21): e10828.
8
Sun K, Guo J, Yao X, et al. Growth differentiation factor 5 in cartilage and osteoarthritis: A possible therapeutic candidate [J]. Cell Prolif, 2021, 54(3): e12998.
9
Norris, M J, Simpson, et al. A modified Newcastle,Ottawa scale for assessment of study quality in genetic urological research [J]. Eur Urol, 2021, 79(3): 325-326.
10
Miyamoto Y, Mabuchi A, Shi DQ, et al. A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis [J]. Nat Genet, 2007, 39(4): 529-533.
11
Southam L, Rodriguez-Lopez J, Wilkins JM, et al. An SNP in the 5'-UTR of GDF5 is associated with osteoarthritis susceptibility in Europeans and with in vivo differences in allelic expression in articular cartilage [J]. Hum Mol Genet, 2007, 16(18): 2226-2232.
12
Chapman K, Takahashi A, Meulenbelt I, et al. A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5' UTR of GDF5 with osteoarthritis susceptibility [J]. Hum Mol Genet, 2008, 17(10): 1497-1504.
13
Tsezou A, Satra M, Oikonomou P, et al. The growth differentiation factor 5 (GDF5) core promoter polymorphism is not associated with knee osteoarthritis in the Greek population [J]. J Orthop Res, 2008, 26(1): 136-140.
14
姚晨,戴进,秦江辉,等. GDF5基因5′端一功能性SNP与骨性关节炎易感性相关[J].江苏医药, 2008, 34(12): 1198-1199.
15
Vaes RBA, 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 [J]. Ann Rheum Dis, 2009, 68(11): 1754-1760.
16
Valdes AM, Spector TD, Doherty S, et al. Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations [J]. Ann Rheum Dis, 2009, 68(12): 1916-1920.
17
Cao Z, Lee HS, Song JH, et al. Growth differentiation factor 5Core promoter polymorphism is not associated with susceptibility to osteoarthritis of the knee in the Korean population [J]. Korean J Pathol, 2010, 44(4): 9.
18
Takahashi H, Nakajima M, Ozaki K, et al. Prediction model for knee osteoarthritis based on genetic and clinical information [J]. Arthritis Res Ther, 2010, 12(5): R187.
19
Tawonsawatruk Tulyapruek, Changthong Theeraroj, Pingsuthiwong Sarinee, et al. A genetic association study between growth differentiation factor 5 (GDF 5) polymorphism and knee osteoarthritis in Thai population [J]. J Orthop Surg Res, 2011, 6: 47.
20
Shin MH, Lee SJ, Kee SJ, et al. Genetic association analysis of GDF5 and Adam12 for knee osteoarthritis [J]. Joint Bone Spine, 2012, 79(5): 488-491.
21
Abd Elazeem MI, Abdelaleem EA, Mohamed RA. Genetic influence of growth and differentiation factor 5 gene polymorphism (+104T/C) on the development of knee osteoarthritis and its association with disease severity [J]. Eur J Rheumatol, 2017, 4(2): 98-103.
22
Mishra A, Srivastava RN, Awasthi S, et al. Expression of genes and their polymorphism influences the risk of knee osteoarthritis [J]. J Nucleic Acids, 2017, 2017: 3138254.
23
Ozcan SS, Korkmaz M, Balbaloglu O, et al. Polymorphisms in the growth differentiation factor 5 (GDF 5) gene in knee osteoarthritis [J]. J Coll Physicians Surg Pak, 2017, 27(10): 602-605.
24
Mohasseb DMF, Saba EKA, Saad NLM, et al. Genetic association between growth differentiation factor 5 single nucleotide polymorphism and primary knee osteoarthritis in a group of Egyptian patients: a pilot study [J]. Mediterr J Rheumatol, 2019, 30(2): 114-122.
25
Zhang SJ, Wang J, Ji HL, et al. Interaction between GDF5 gene polymorphisms and environment factors increased the risk of knee osteoarthritis: a case-control study [J]. Biosci Rep, 2019, 39(2): BSR20182423.
26
Jia B, Jiang YP, Xu YX, et al. Correlation between growth differentiation factor 5 (rs143383) gene polymorphism and knee osteoarthritis: an updated systematic review and meta-analysis [J]. J Orthop Surg Res, 2021, 16(1): 146.
27
杨明义,苏亚妮,郑海石,等.骨性关节炎软骨下骨改变中的潜在生物标志物[J].中华实验外科杂志, 2022, 39(4): 749-752.
28
顾晓东,车先达,李鹏翠,等.骨关节炎基因治疗的研究进展[J].中华骨与关节外科杂志, 2019, 12(05): 396-400.
29
Beier F. The impact of omics research on our understanding of osteoarthritis and future treatments [J]. Curr Opin Rheumatol, 2023, 35(1): 55-60.
30
Pothiawala A, Sahbazoglu BE, Ang BK, et al. GDF5+ chondroprogenitors derived from human pluripotent stem cells preferentially form permanent chondrocytes [J]. Development, 2022, 149(11): 196220.
31
Hata A, Seoane J, Lagna G, et al. OAZ uses distinct DNA- and protein-binding Zinc fingers in separate BMP-Smad and Olf signaling pathways [J]. Cell, 2000, 100(2): 229-240.
32
Aoki H, Fujii M, Imamura T, et al. Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction [J]. J Cell Sci, 2001, 114(Pt 8): 1483-1489.
33
He Y, Yao W, Zhang M, et al. Changes in osteogenic gene expression in hypertrophic chondrocytes induced by SIN-1 [J]. Exp Ther Med, 2018, 16(2): 609-618.
34
Schwaerzer GK, Hiepen C, Schrewe H, et al. New insights into the molecular mechanism of multiple synostoses syndrome (SYNS): mutation within the GDF5 knuckle epitope causes noggin-resistance [J]. J Bone Miner Res, 2012, 27(2): 429-442.
35
Zhang WT, Wu XH, Pei Z, et al. GDF5 promotes white adipose tissue thermogenesis via p38 MAPK signaling pathway [J]. DNA Cell Biol, 2019, 38(11): 1303-1312.
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