Öz
Amaç: Embriyo implantasyonu ve plasental dolaşımın temel sorumlusu olan kapiller damarlardaki patolojilerin abortus etiyolojisindeki mekanizmalar üzerinde etkileri olduğu bilinmektedir. Matriks metalloproteinaz (MMP) ailesinden MMP2 ve MMP9’un ekstrasellüler matriks organizasyonunda ve trofoblast implantasyonunda önemli görevleri vardır. Bu çalışmada, fonksiyonel olduğu bilinen MMP2 -735 C>T, -1306 C>T ve MMP9 -1562 C>T polimorfizmlerinin spontan abortus (SA) materyallerindeki genotip farklılıklarını belirlemek ve bu polimorfizmlerin SA etiyolojisinde rolü olup olmadığına ışık tutabilmek amaçlanmıştır.
Gereç ve Yöntem: Polimorfizmlerin genotiplerinin analizinde restriksiyon fragman uzunluk polimorfizmi (RFLP) yöntemi kullanılmıştır. Çalışma grubu 80 spontan abortus örneğinden, kontrol grubu 100 sağlıklı gönüllü bireyin periferik kan örneğinden oluşmaktadır.
Bulgular: MMP2 -735 C>T ve MMP9 -1562 C>T polimorfizmleri için SA örnekleri ve kontrol grubu arasında anlamlı fark saptanmadı. MMP2 -1306 C>T polimorfizminin heterozigot genotip sıklığı SA örneklerinde kontrol grubuna kıyasla 2,2 kat daha fazla bulundu (p=0.043). MMP2 genindeki normal -735 C>T ve heterozigot -1306 C>T genotiplerinin birlikte görülme sıklığı SA örneklerinde kontrol grubuna göre 3,7 kat fazla idi (p=0.021).
Sonuç: MMP2 -1306 C>T fonksiyonel polimorfizmi ile SA oluşması arasında bir ilişki bulunmuştur. Daha yüksek sayılardaki SA çalışmalarındaki ileri genetik çalışmalar ve ekspresyon analizleri MMP2 ve MMP9 polimorfizmlerinin SA üzerindeki potansiyel rollerini net olarak belirlemede katkıda bulunacaktır.
Anahtar Kelimeler
Kaynakça
- Quenby S, Gallos ID, Dhillon-Smith RK, Podesek M, Stephenson MD, Fisher J, Brosens JJ, ve ark. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet. 2021; 397 (10285): 1658-67.
- Committee on Practice Bulletins—Gynecology. The American College of Obstetricians and Gynecologists Practice Bulletin no. 150. Early pregnancy loss. Obstet Gynecol. 2015 May;125(5):1258-67.
- Muter J, Lynch VJ, McCoy RC, Brosens JJ. Human embryo implantation. Development. 2023; 150 (10): dev201507.
- Huang HY. The cytokine network during embryo implantation. Chang Gung Med J. 2006; 29 (1): 25-36.
- Knapinska A, Fields GB. Chemical biology for understanding matrix metalloproteinase function. Chembiochem 2012; 13 (14): 2002-20.
- Hisamatsu Y, Murata H, Tsubokura H, Hashimoto Y, Kitada M, Tanaka S, Okada H. Matrix Metalloproteinases in Human Decidualized Endometrial Stromal Cells. Curr Issues Mol Biol 2021 ;43 (3): 2111-23.
- Sharma S, Godbole G, Modi D. Decidual Control of Trophoblast Invasion. Am J Reprod Immunol 2016; 75 (3): 341-50.
- Yılmaz F, Tekmen I. İmplantasyon Sürecinde Embriyo, Endometriyum Farklanması ve Moleküler Yolaklar. Turkiye Klinikleri J Med Sci 2019; 39 (2): 212-20.
- Nissi R, Talvensaari-Mattila A, Kotila V, Niinimäki M, Järvela I, Turpeenniemi-Hujanen T. Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure. Reprod Biol Endocrinol 2013; 11: 2.
- Jiang G, Qi Y. Detection of MMP-9 and TIMP-3 mRNA expression in the villi of patients undergoing early spontaneous abortion: A report of 30 cases. Exp Ther Med 2015; 9 (5): 1939-43.
- Pereza N, Ostoj c S, Volk M, Kapov c M, Peterl n B. Matr metalloprote nases 1, 2, 3 and 9 funct onal single-nucleotide polymorphisms in idiopathic recurrent spontaneous abortion. Reprod BioMed Online 2012; 24 (5): 567–75.
- Chen J, Khalil RA. Matrix metalloproteinases in normal pregnancy and preeclampsia. Prog Mol Biol Transl Sci. 2017; 148: 87-165.
- Li L, Liu J, Qin S, Li R. The association of polymorphisms in promoter region of MMP2 and MMP9 with recurrent spontaneous abortion risk in Chinese population. Medicine (Baltimore). 2018; 97 (40): e12561.
- Ramu D, Venkatesan V, Paul SFD, Koshy T. Genetic variation in matrix metalloproteinase MMP2 and MMP9 as a risk factor for idiopathic recurrent spontaneous abortions in an Indian population. J Assist Reprod Genet. 2017; 34 (7): 945-9.
- Gremlich S, Nguyen D, Reymondin D, Hohlfeld P, Vial Y, Witkin SS, Gerber S. Fetal MMP2/MMP9 polymorphisms and intrauterine growth restriction risk. Journal of Reproductive Immunology, 2007, 23:143 51.
Öz
Aim: It is known that pathologies related to capillaries, which are responsible for maintenance of implantation and placental nutrition, have effects on mechanisms underlying abortion. Matrix metalloproteinase 2 and 9 (MMP2 and MMP9) 2, which are members of MMP family, having key roles at organisation of extracellular matrix and endometrial trophoblast implantation. The aim of this study was to investigate the frequencies of functional MMP2 -735 C>T, -1306 C>T and MMP9 -1562 C>T polymorphisms in spontaneous abortion (SA) materials.
Materials and Methods: Restriction fragment length polymorphism (RFLP) was used to analyze the genotypes of these polymorphisms. Study group consisted of samples collected from 80 SA specimens, and control group consisted of peripheral blood samples collected from 100 healthy subjects.
Results: There was no significant difference between SA samples and control group for MMP2 -735 C>T and MMP9 -1562 C>T polymorphisms. Frequency of heterozygous MMP2 -1306 C>T genotype was 2.2-fold higher in SA samples compared to control group (p=0.043). Coexistence of normal MMP2 -735 C>T genotype and heterozygous -1306 C>T genotype was 3.7-fold higher in SA samples compared to control group (p=0.021).
Conclusion: MMP2 -1306 C>T functional polymorphism have a role in spontaneous abortion. Further genetic studies on a larger number of SA samples and expression analysis of the genes may contribute to determining potential roles of MMP2 and MMP9 polymorphisms in SA.
Anahtar Kelimeler
Kaynakça
- Quenby S, Gallos ID, Dhillon-Smith RK, Podesek M, Stephenson MD, Fisher J, Brosens JJ, ve ark. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet. 2021; 397 (10285): 1658-67.
- Committee on Practice Bulletins—Gynecology. The American College of Obstetricians and Gynecologists Practice Bulletin no. 150. Early pregnancy loss. Obstet Gynecol. 2015 May;125(5):1258-67.
- Muter J, Lynch VJ, McCoy RC, Brosens JJ. Human embryo implantation. Development. 2023; 150 (10): dev201507.
- Huang HY. The cytokine network during embryo implantation. Chang Gung Med J. 2006; 29 (1): 25-36.
- Knapinska A, Fields GB. Chemical biology for understanding matrix metalloproteinase function. Chembiochem 2012; 13 (14): 2002-20.
- Hisamatsu Y, Murata H, Tsubokura H, Hashimoto Y, Kitada M, Tanaka S, Okada H. Matrix Metalloproteinases in Human Decidualized Endometrial Stromal Cells. Curr Issues Mol Biol 2021 ;43 (3): 2111-23.
- Sharma S, Godbole G, Modi D. Decidual Control of Trophoblast Invasion. Am J Reprod Immunol 2016; 75 (3): 341-50.
- Yılmaz F, Tekmen I. İmplantasyon Sürecinde Embriyo, Endometriyum Farklanması ve Moleküler Yolaklar. Turkiye Klinikleri J Med Sci 2019; 39 (2): 212-20.
- Nissi R, Talvensaari-Mattila A, Kotila V, Niinimäki M, Järvela I, Turpeenniemi-Hujanen T. Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure. Reprod Biol Endocrinol 2013; 11: 2.
- Jiang G, Qi Y. Detection of MMP-9 and TIMP-3 mRNA expression in the villi of patients undergoing early spontaneous abortion: A report of 30 cases. Exp Ther Med 2015; 9 (5): 1939-43.
- Pereza N, Ostoj c S, Volk M, Kapov c M, Peterl n B. Matr metalloprote nases 1, 2, 3 and 9 funct onal single-nucleotide polymorphisms in idiopathic recurrent spontaneous abortion. Reprod BioMed Online 2012; 24 (5): 567–75.
- Chen J, Khalil RA. Matrix metalloproteinases in normal pregnancy and preeclampsia. Prog Mol Biol Transl Sci. 2017; 148: 87-165.
- Li L, Liu J, Qin S, Li R. The association of polymorphisms in promoter region of MMP2 and MMP9 with recurrent spontaneous abortion risk in Chinese population. Medicine (Baltimore). 2018; 97 (40): e12561.
- Ramu D, Venkatesan V, Paul SFD, Koshy T. Genetic variation in matrix metalloproteinase MMP2 and MMP9 as a risk factor for idiopathic recurrent spontaneous abortions in an Indian population. J Assist Reprod Genet. 2017; 34 (7): 945-9.
- Gremlich S, Nguyen D, Reymondin D, Hohlfeld P, Vial Y, Witkin SS, Gerber S. Fetal MMP2/MMP9 polymorphisms and intrauterine growth restriction risk. Journal of Reproductive Immunology, 2007, 23:143 51.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 10 Haziran 2024 |
| Gönderilme Tarihi | 9 Mart 2023 |
| Yayımlandığı Sayı | Yıl 2024 |