Association between the insertion/deletion polymorphism of ACE gene and osteoarthritis: a meta-analysis and trial sequential analysis_Chinese Journal of Evidence-Based Medicine

Authors：

CHEN Lei ^{1, 2, #} , AI Jinwei ^{1, 2, #} , LAN Shan ¹ , TANG Lingling ¹ , WU Wenfeng ¹ ,  PEI Bin ^{1, 2}

1. Evidence-Based Medicine Center, Xiangyang No.1 people's Hospital, Hubei University of Medicine, Xiangyang, 441000, P.R.China;
2. Department of Orthopaedics, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, 441000, P.R.China;

Corresponding?author：

PEI Bin, Email: xyxzyxzx@163.com

Keywords：

Peptidyl-dipeptidase A; Polymorphism, genetic; Osteoarthritis; Meta-analysis; Trial sequential analysis

DOI：

10.7507/1672-2531.201610053

Video：

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ObjectiveTo systematically review the association between angiotension-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and osteoarthritis (OA) by using meta-analysis and trial sequential analysis (TSA). MethodsThe PubMed, EMbase, CNKI, CBM, VIP, and WanFang Data were searched up to October 12^th, 2016 for case-control or cohort studies on the correlation between ACE I/D polymorphism and OA risk. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis and TSA analysis were performed using Stata 13.1 software and TSA v0.9 soft ware. ResultsA total of six case-control studies involving 1 165 OA patients and 1 029 controls were included. The results of meta-analysis showed that the ACE I/D was associated with OA risk (DD+DI vs. II: OR=1.72, 95%CI 1.02 to 2.90, P=0.04; DI vs. II: OR=1.65, 95%CI 1.06 to 2.56, P=0.03). Subgroup analysis of ethnicity showed that, in Caucasians, the ACE I/D was associated with OA risk (DD vs. DI+II: OR=2.10, 95%CI 1.54 to 2.85, P<0.01; DD+DI vs. II: OR=3.11, 95%CI 2.20 to 4.39, P<0.01; DD vs. II: OR=4.01, 95%CI 2.68 to 6.00, P<0.01; DI vs. II: OR=2.65, 95%CI 1.06 to 2.56, P<0.01; D vs. I: OR=2.11, 95%CI 1.72 to 2.58, P=0.73). And TSA showed that all of the cumulative Z-curve strode the conventional and TSA threshold value which suggested the result of the association between ACE I/D polymorphism and OA in Caucasians was very reliable. However, the association did not exist in Asians (DD vs. DI+II: OR=0.80, 95%CI 0.60 to 1.07, P=0.13; DD+DI vs. II: OR=1.08, 95%CI 0.87 to 1.35, P=0.49; DD vs. II: OR=0.86, 95%CI 0.62 to 1.20, P=0.38; DI vs. II: OR=1.18, 95%CI 0.93 to 1.50, P=0.19; D vs. I: OR=0.93, 95%CI 0.83 to 1.14, P=0.73). And the results of TSA displayed that all of the cumulative Z-curve did not strode both TSA threshold value and required information size line excepting for DD vs. DI+II genetic model which suggested that the sample-size in Asians was insufficient. ConclusionsThe ACE D allele maybe a risk factor for OA in Caucasians. However, the association between ACE I/D polymorphism and OA risk in Asians still need more studies to prove.

Citation： CHENLei, AIJinwei, LANShan, TANGLingling, WUWenfeng, PEIBin. Association between the insertion/deletion polymorphism of ACE gene and osteoarthritis: a meta-analysis and trial sequential analysis. Chinese Journal of Evidence-Based Medicine, 2017, 17(2): 135-143. doi: 10.7507/1672-2531.201610053 Copy

1.	?Altman R, Schemitsch E, Bedi A. Assessment of clinical practice guideline methodology for the treatment of knee osteoarthritis with intra-articular hyaluronic acid. Semin Arthritis Rheum, 2015, 45(2): 132-139.
2.	Cutolo M, Berenbaum F, Hochberg M, et al. Commentary on recent therapeutic guidelines for osteoarthritis. Semin Arthritis Rheum, 2015, 44(6): 611-617.
3.	Silverwood V, Blagojevic-Bucknall M, Jinks C, et al. Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage, 2015, 23(4): 507-515.
4.	劉羽, 艾金偉, 劉盈, 等. 中醫療法與透明質酸治療膝骨性關節炎有效性的網狀 Meta 分析. 中國組織工程研究. 2016, 20(20): 3000-3011.
5.	Apold H, Meyer HE, Nordsletten L, et al. Risk factors for knee replacement due to primary osteoarthritis, a population based, prospective cohort study of 315,495 individuals. BMC Musculoskelet Disord, 2014, 15: 217.
6.	Evangelou E, Kerkhof H, Styrkarsdottir U, et al. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip. Ann Rheum Dis, 2014, 73(12): 2130-2136.
7.	Hunter DJ, March L, Sambrook PN. Knee osteoarthritis: The influence of environmental factors. Clin Exp Rheumatol. 2002, 20(201): 93-100.
8.	Sayed-Tabatabaei F. ACE polymorphisms. Circ Res, 2006, 98(9): 1123-1133.
9.	Blann A. von Willebrand factor antigen and angiotensin converting enzyme in synovial fluid. Scand J Rheumatol, 1991, 20(3): 213-214.
10.	Cerinic M, Lombardi A, Leoncini G, et al. Neutral endopeptidase (3.4.24.11) in plasma and synovial fluid of patients with rheumatoid arthritis. A marker of disease activity or a regulator of pain and inflammation? Rheumatol Int, 1993, 13(1): 1-4.
11.	Moher D, Liberati A, Tetzlaff J, et al. Reprint--preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther, 2009, 89(9): 873-880.
12.	Zeng X, Zhang Y, Kwong JS, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med, 2015, 8(1): 2-10.
13.	翁鴻, 李勝, 曾憲濤, 等. 試驗序貫分析軟件在Meta分析中的應用. 中國循證醫學雜志, 2016, 16(5): 604-611.
14.	王權, 田金微, 李倫, 等. 試驗序貫分析簡介. 中國循證醫學雜志, 2013, 13(10): 1265-1268.
15.	Hong S, Yang H, Yoo M, et al. Angiotensin converting enzyme gene polymorphism in Korean patients with primary knee osteoarthritis. Exp Mol Med, 2003, 35(3): 189-195.
16.	Shehab D, Al-Jarallah K, Alawadhi A, et al. Prevalence of angiotensin-converting enzyme gene insertion-deletion polymorphism in patients with primary knee osteoarthritis. Clin Exp Rheumatol, 2008, 26(2): 305-310.
17.	Lin C, Chen HC, Fang WH, et al. Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis. PLoS ONE, 2016, 11(9): e161754.
18.	Bayram B, Say?n E, Gunes H, et al. DD genotype of ace gene I/D polymorphism is associated in a turkish study.
19.	Inanir A, Yigit S, Tural S, et al. MTHFR gene C677T mutation and ACE gene I/D polymorphism in Turkish patients with osteoarthritis. Dis Markers, 2013, 34: 17-22.
20.	Poornima S, Subramanyam K, Khan I A, et al. The insertion and deletion (I28005D) polymorphism of the angiotensin I converting enzyme gene is a risk factor for osteoarthritis in an Asian Indian population. J Renin Angiotensin Aldosterone Sys, 2014, Suppl(1): 1-7.
21.	王權, 田金微, 李倫, 等. 試驗序貫分析與meta 分析所需樣本量的估算. 蘭州大學學報(醫學版), 2015, 41(4): 76-80.
22.	夏蕓, 孫瑛, 劉兆蘭, 等. 系統綜述或Meta分析的樣本量估算—試驗序貫分析. 北京中醫藥大學學報(中醫臨床版), 2013, 20(5): 31-33.
23.	Shi D, Zheng Q, Chen D, et al. Association of single-nucleotide polymorphisms in HLA class II/III region with knee osteoarthritis. Osteoarthr Cartilage, 2010, 18(11): 1454-1457.
24.	艾金偉, 劉盈, 李德勝, 等. ACE 基因插入/缺失多態性與運動員力量型運動能力關聯性的 Meta 分析. 中國循證醫學雜志, 2016, 16(3): 263-269.
25.	艾金偉, 劉盈, 李德勝, 等. ACE 基因插入/缺失多態性與運動員耐力型運動能力關聯性的 Meta 分析, 中國循證醫學雜志, 2016, 16(4): 392-402.
26.	Tiret L, Rigat B, Visvikis S, et al. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet, 1992, 51(1): 197-205.
27.	Mizuiri S, Shimatake H, Hasegawa A, et al. Angiotensin-converting enzyme (ACE) I/D genotype and renal ACE gene expression. Kidney Int, 2001, 60(3): 1124-1130.
28.	Poole A R, Ionescu M, Swan A, et al. Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis. J Clin Invest, 1994, 94(1): 25-33.
29.	Cassim B, Mody G, Bhoola K. Kallikrein cascade and cytokines in inflamed joints. Pharmacol Ther, 2002, 94(1-2): 1-34.
30.	Cassim B, Naidoo S, Ramsaroop R, et al. Immunolocalization of bradykinin receptors on human synovial tissue. Immunopharmacol, 1997, 36(2): 121-125.

1. ?Altman R, Schemitsch E, Bedi A. Assessment of clinical practice guideline methodology for the treatment of knee osteoarthritis with intra-articular hyaluronic acid. Semin Arthritis Rheum, 2015, 45(2): 132-139.
2. Cutolo M, Berenbaum F, Hochberg M, et al. Commentary on recent therapeutic guidelines for osteoarthritis. Semin Arthritis Rheum, 2015, 44(6): 611-617.
3. Silverwood V, Blagojevic-Bucknall M, Jinks C, et al. Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage, 2015, 23(4): 507-515.
4. 劉羽, 艾金偉, 劉盈, 等. 中醫療法與透明質酸治療膝骨性關節炎有效性的網狀 Meta 分析. 中國組織工程研究. 2016, 20(20): 3000-3011.
5. Apold H, Meyer HE, Nordsletten L, et al. Risk factors for knee replacement due to primary osteoarthritis, a population based, prospective cohort study of 315,495 individuals. BMC Musculoskelet Disord, 2014, 15: 217.
6. Evangelou E, Kerkhof H, Styrkarsdottir U, et al. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip. Ann Rheum Dis, 2014, 73(12): 2130-2136.
7. Hunter DJ, March L, Sambrook PN. Knee osteoarthritis: The influence of environmental factors. Clin Exp Rheumatol. 2002, 20(201): 93-100.
8. Sayed-Tabatabaei F. ACE polymorphisms. Circ Res, 2006, 98(9): 1123-1133.
9. Blann A. von Willebrand factor antigen and angiotensin converting enzyme in synovial fluid. Scand J Rheumatol, 1991, 20(3): 213-214.
10. Cerinic M, Lombardi A, Leoncini G, et al. Neutral endopeptidase (3.4.24.11) in plasma and synovial fluid of patients with rheumatoid arthritis. A marker of disease activity or a regulator of pain and inflammation? Rheumatol Int, 1993, 13(1): 1-4.
11. Moher D, Liberati A, Tetzlaff J, et al. Reprint--preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther, 2009, 89(9): 873-880.
12. Zeng X, Zhang Y, Kwong JS, et al. The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review. J Evid Based Med, 2015, 8(1): 2-10.
13. 翁鴻, 李勝, 曾憲濤, 等. 試驗序貫分析軟件在Meta分析中的應用. 中國循證醫學雜志, 2016, 16(5): 604-611.
14. 王權, 田金微, 李倫, 等. 試驗序貫分析簡介. 中國循證醫學雜志, 2013, 13(10): 1265-1268.
15. Hong S, Yang H, Yoo M, et al. Angiotensin converting enzyme gene polymorphism in Korean patients with primary knee osteoarthritis. Exp Mol Med, 2003, 35(3): 189-195.
16. Shehab D, Al-Jarallah K, Alawadhi A, et al. Prevalence of angiotensin-converting enzyme gene insertion-deletion polymorphism in patients with primary knee osteoarthritis. Clin Exp Rheumatol, 2008, 26(2): 305-310.
17. Lin C, Chen HC, Fang WH, et al. Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis. PLoS ONE, 2016, 11(9): e161754.
18. Bayram B, Say?n E, Gunes H, et al. DD genotype of ace gene I/D polymorphism is associated in a turkish study.
19. Inanir A, Yigit S, Tural S, et al. MTHFR gene C677T mutation and ACE gene I/D polymorphism in Turkish patients with osteoarthritis. Dis Markers, 2013, 34: 17-22.
20. Poornima S, Subramanyam K, Khan I A, et al. The insertion and deletion (I28005D) polymorphism of the angiotensin I converting enzyme gene is a risk factor for osteoarthritis in an Asian Indian population. J Renin Angiotensin Aldosterone Sys, 2014, Suppl(1): 1-7.
21. 王權, 田金微, 李倫, 等. 試驗序貫分析與meta 分析所需樣本量的估算. 蘭州大學學報(醫學版), 2015, 41(4): 76-80.
22. 夏蕓, 孫瑛, 劉兆蘭, 等. 系統綜述或Meta分析的樣本量估算—試驗序貫分析. 北京中醫藥大學學報(中醫臨床版), 2013, 20(5): 31-33.
23. Shi D, Zheng Q, Chen D, et al. Association of single-nucleotide polymorphisms in HLA class II/III region with knee osteoarthritis. Osteoarthr Cartilage, 2010, 18(11): 1454-1457.
24. 艾金偉, 劉盈, 李德勝, 等. ACE 基因插入/缺失多態性與運動員力量型運動能力關聯性的 Meta 分析. 中國循證醫學雜志, 2016, 16(3): 263-269.
25. 艾金偉, 劉盈, 李德勝, 等. ACE 基因插入/缺失多態性與運動員耐力型運動能力關聯性的 Meta 分析, 中國循證醫學雜志, 2016, 16(4): 392-402.
26. Tiret L, Rigat B, Visvikis S, et al. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet, 1992, 51(1): 197-205.
27. Mizuiri S, Shimatake H, Hasegawa A, et al. Angiotensin-converting enzyme (ACE) I/D genotype and renal ACE gene expression. Kidney Int, 2001, 60(3): 1124-1130.
28. Poole A R, Ionescu M, Swan A, et al. Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis. J Clin Invest, 1994, 94(1): 25-33.
29. Cassim B, Mody G, Bhoola K. Kallikrein cascade and cytokines in inflamed joints. Pharmacol Ther, 2002, 94(1-2): 1-34.
30. Cassim B, Naidoo S, Ramsaroop R, et al. Immunolocalization of bradykinin receptors on human synovial tissue. Immunopharmacol, 1997, 36(2): 121-125.

Chinese Journal of Evidence-Based Medicine

Association between the insertion/deletion polymorphism of ACE gene and osteoarthritis: a meta-analysis and trial sequential analysis

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