Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study

Çelik, Zülfinaz Betül; Tural, Ercan; TEKCAN, ESRA; tural, sengul

doi:10.5505/vtd.2023.88864

Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study

Ercan TURAL, (Ondokuz Mayıs Üniversitesi, Sağlık Bilimleri Fakültesi, Fizyoterapi ve Rehabilitasyon Bölümü, Samsun, Türkiye)

Zülfinaz Betül ÇELİK, (Samsun Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji Anabilim Dalı, Samsun, Türkiye)

Esra TEKCAN, (Ondokuz Mayıs Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji Anabilim Dalı, Samsun, Türkiye)

Şengül TURAL (Ondokuz Mayıs Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji Anabilim Dalı, Samsun, Türkiye)

Van Tıp Dergisi

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Yıl: 2023 Cilt: 30 Sayı: 1 Sayfa Aralığı: 22 - 26 Metin Dili: İngilizce DOI: 10.5505/vtd.2023.88864 İndeks Tarihi: 04-05-2023

Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study

Öz:

Introduction: In this study, we aimed to examine the relationship between the MMP-3 gene promoter methylation status and the risk of developing achilles tendinitis in endurance athletes. Materials and Methods: A total of 20 endurance athletes with achille tendonitis and 20 sedantary controls were involved in the study. DNA isolation and bisulfite modification were performed from peripheral blood samples of all volunteers. Using methylation-specific primers designed for MMP-3 gene promoters, methylation profiles were analyzed by the methylation specific polymerase chain reaction method. Results: In the MMP-3 gene promoter methylation analysis, the methylation frequency was found to be 75% in athletes with Achilles tendinitis, while it was found to be 100% in the control group. MMP-3 promoter region methylation status in the patient group was found to be hypomethylated compared to the control group. Discussion and Conclusion: The hypomethylated status of the MMP-3 gene promoter may have a role in developing achilles tendonitis in athletes. Furher and larges studies are needed to confirm our results.

Anahtar Kelime:

Matriks Metalloproteinaz-3 (MMP-3) Geni Metilasyon Durumunun Aşil Tendinit Gelişmi Riski ile İlişkisi: Bir Ön Çalışma

Öz:

Giriş: Bu çalışmada, MMP-3 geni promotör metilasyon durumu ile dayanıklılık sporu ile uğraşan bireylerde aşil tendinit gelişimi riski arasındaki ilişkiyi incelemeyi amaçladık. Gereç ve Yöntem: Çalışmaya aşil tendinitli toplam 20 sporcu ve 20 sedanter kontrol dahil edildi. Tüm gönüllülerin periferik kan örneklerinden DNA izolasyonu ve bisülfit modifikasyonu yapıldı. Daha sonra MMP-3 gen promotörleri için tasarlanmış metilasyona özgü primerler kullanılarak metilasyon profilleri, metilasyona özgü polimeraz zincir reaksiyonu yöntemiyle analiz edildi. Bulgular: MMP-3 gen promotörü metiasyon analizinde, aşil tendiniti olan sporcularda metilasyon sıklığı %75 olarak saptanırken, kontrol grubunda %100 olarak bulundu (p<0.05). Hasta grubunda MMP-3 promotör bölge metilasyon durumu kontrol grubuna göre hipometile olarak saptandı. Sonuç: Sonuçlarımıza göre MMP-3 gen promotörünün hipometile durumu, sporcularda aşil tendinit gelişiminde rol oynuyor olabilir. Sonuçlarımızı doğrulamak için daha fazla ve daha büyük çalışmalara ihtiyaç vardır.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Guo R, Aizezi A, Fan Y, Ji Z, Li W, Li Y, et al. Association between matrixmetalloproteinase-3 gene polymorphisms and tendon-ligament injuries: evidence from a meta-analysis. BMC Sports Sci Med Rehabil 2022 16;14(1):26.
2. Ackermann PW and Renström P. Tendinopathy in Sport. Sports Health 2012;3(4):193-201.
3. Reinking M. Tendinopathy in athletes. Phys Ther Sport 2012;13(1):3-10.
4. Maffuli N, Margiotti K, Longo UG, Loppini M, Fazio VM, Denaro V. The genetics of sports injuries and athletic performance. Muscles Ligaments Tendons J 2013; 3(3):173-189.
5. Thankam FG, Boosani CS, Dilisio MF, Agrawal DK. Epigenetic mechanisms and implications in tendon inflammation. Int J Mol Med 2019;43:3-14.
6. Leal MF, DosSantos LC, De Oliveira AM, Balengero PS, Figueiredo EA, Cohen C, et al. Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears. PLoS One 2017;12(9):0184141.
7. Somerville RP, Oblander SA, Apte SS. Matrix metalloproteinases: old dogs with new tricks. Genome Biol 2003;4(6):1-11.
8. Raleigh SM. Epigenetic regulation of the ACE gene might be more relevant to endurance physiology than the I/D polymorphism. J Appl Physiol 2012;112(6):1082-1083.
9. Foster BP, Morse CI, Onambele GL, Ahmetov II, Williams AG. Genetic Variation, Protein Composition and Potential Influences on Tendon Properties in Humans. J Sports Med 2012;6:8-21.
10. Rickaby R, El Khoury LY, Samiric T, Raleigh SM. Epigenetic Status of The Human MMP11 Gene Promoter is Altered in Patellar Tendinopathy. J Sports Sci Med 2019;18:155-159.
11. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry. Circ Res 2003;92(8):827-839.,
12. Collins M, Raleigh SM. Genetic risk factors for musculoskeletal soft tissue injuries. Genetics and Sports 2009;54: 136-149.
13. Briski N, Vrgoc G, Knjaz D, Jankovic S, Ivkovic A, Pecina, M, et al. Association of the matrix metalloproteinase 3 (MMP-3) single nucleotide polymorphisms with tendinopathies: case-control study in highlevel athletes. Int Orthop. 2021 45(5):1163- 1168.
14. Nie G, Wen X, Liang X, Zhao H, Li Y, Lu J. Additional evidence supports association of common genetic variants in MMP-3 and TIMP2 with increased risk of chronic Achilles tendinopathy susceptibility. J Sci Med Sport 2019;22(10):1074-1078.
15. El Khoury L, Ribbans WJ, & Raleigh SM. MMP3 and TIMP2 gene variants as predisposing factors for Achilles tendon pathologies: Attempted replication study in a British case–control cohort. Meta Gene. 2016 Mar 30;9:52-5.
16. Foster BP, Morse CI, Onambele GL, Williams AG. Variants within the MMP3 gene and patellar tendon properties in vivo in an asymptomatic population. Eur J Appl Physiol 2014;114(12):2625-2634.
17. Celik ZB, Tural S, Cengiz AK, Kara N, Alayli G. Upregulation of microRNA-93- 5p/microRNA-4668-5p, and promoter methylation of matrix metalloproteinase-3 and interleukin-16 genes in Turkish patients with Rheumatoid Arthritis. Egypt Rheumatol 2021;43(1):35-39.

APA	Tural E, Çelik Z, TEKCAN E, tural s (2023). Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study. , 22 - 26. 10.5505/vtd.2023.88864
Chicago	Tural Ercan,Çelik Zülfinaz Betül,TEKCAN ESRA,tural sengul Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study. (2023): 22 - 26. 10.5505/vtd.2023.88864
MLA	Tural Ercan,Çelik Zülfinaz Betül,TEKCAN ESRA,tural sengul Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study. , 2023, ss.22 - 26. 10.5505/vtd.2023.88864
AMA	Tural E,Çelik Z,TEKCAN E,tural s Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study. . 2023; 22 - 26. 10.5505/vtd.2023.88864
Vancouver	Tural E,Çelik Z,TEKCAN E,tural s Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study. . 2023; 22 - 26. 10.5505/vtd.2023.88864
IEEE	Tural E,Çelik Z,TEKCAN E,tural s "Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study." , ss.22 - 26, 2023. 10.5505/vtd.2023.88864
ISNAD	Tural, Ercan vd. "Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study". (2023), 22-26. https://doi.org/10.5505/vtd.2023.88864

APA	Tural E, Çelik Z, TEKCAN E, tural s (2023). Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study. Van Tıp Dergisi, 30(1), 22 - 26. 10.5505/vtd.2023.88864
Chicago	Tural Ercan,Çelik Zülfinaz Betül,TEKCAN ESRA,tural sengul Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study. Van Tıp Dergisi 30, no.1 (2023): 22 - 26. 10.5505/vtd.2023.88864
MLA	Tural Ercan,Çelik Zülfinaz Betül,TEKCAN ESRA,tural sengul Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study. Van Tıp Dergisi, vol.30, no.1, 2023, ss.22 - 26. 10.5505/vtd.2023.88864
AMA	Tural E,Çelik Z,TEKCAN E,tural s Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study. Van Tıp Dergisi. 2023; 30(1): 22 - 26. 10.5505/vtd.2023.88864
Vancouver	Tural E,Çelik Z,TEKCAN E,tural s Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study. Van Tıp Dergisi. 2023; 30(1): 22 - 26. 10.5505/vtd.2023.88864
IEEE	Tural E,Çelik Z,TEKCAN E,tural s "Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study." Van Tıp Dergisi, 30, ss.22 - 26, 2023. 10.5505/vtd.2023.88864
ISNAD	Tural, Ercan vd. "Association of Matrix Metalloproteinase-3 (MMP-3) Gene Methylation Status with the Risk of Developing Achilles Tendonitis: A Preliminary Study". Van Tıp Dergisi 30/1 (2023), 22-26. https://doi.org/10.5505/vtd.2023.88864