THE MMP9 −1562 C/T POLYMORPHISM IS ASSOCIATED WITH INCREASED RISK OF DIABETIC RETINOPATHY IN TURKISH TYPE 2 DIABETES MELLITUS PATIENTS
Öz
Objective
Type 2 diabetes mellitus (T2DM) and diabetic
retinopathy (DR) development is affected by genetic
factors. Matrix metalloproteinases (MMPs) are involved
in many cellular processes, such as remodeling of
extracellular matrix proteins and angiogenesis. In
this study, we investigated the relationship between
MMP9 −1562 C/T (rs3918242) polymorphism and the
development of T2DM and DR in Turkish population.
Material and Method
A total of 510 participants, involving 168 T2DM
cases with DR, 168 T2DM cases without DR,
and 174 controls, were included in the study. The
polymerase chain reaction-restriction fragment length
polymorphism (PCR-RFLP) method was carried out
to identify genotypes.
Results
The CT, CT+TT genotypes and the T allele of the
MMP9 −1562 C/T polymorphism were associated with
increased risk of DR (p=0.001). On the other hand,
no relationship was found between the development
of T2DM and this polymorphism. In addition,
CT (p=0.010) and CT+TT (p=0.015) genotype
frequencies were found to be higher in proliferative
diabetic retinopathy (PDR) cases compared to nonproliferative
diabetic retinopathy (NPDR) cases, but
after regression analysis, only insulin use (p=0.003)
was found to be associated with the development of
PDR.
Conclusion
Our data show that the MMP9 −1562 C/T polymorphism
is associated with the development of DR in Turkish
T2DM patients, but no significant relationship was
found between this polymorphism and the severity of
DR and the development of T2DM.
Anahtar Kelimeler
MMP9 Diabetic retinopathy proliferative diabetic retinopathy type 2 diabetes mellitus polymorphism
Kaynakça
- 1. Simó-Servat O, Hernández C, Simó R. Diabetic Retinopathy in the Context of Patients with Diabetes. Ophthalmic Res 2019;62(4):211–7.
- 2. Han J, Lando L, Skowronska-Krawczyk D, Chao DL. Genetics of Diabetic Retinopathy. Curr Diab Rep. 2019;19(9):67.
- 3. Kowluru RA, Mishra M. Regulation of Matrix Metalloproteinase in the Pathogenesis of Diabetic Retinopathy. Prog Mol Biol Transl Sci 2017;148:67–85.
- 4. Bhatwadekar AD, Shughoury A, Belamkar A, Ciulla TA. Genetics of Diabetic Retinopathy, a Leading Cause of Irreversible Blindness in the Industrialized World. Genes (Basel) 2021;12(8):1200.
- 5. Browning DJ, Stewart MW, Lee C. Diabetic macular edema: Evidence-based management. Indian J Ophthalmol 2018;66(12):1736.
- 6. Simó R, Vujosevic S, Aldington SJ, Silva P, Hernández C, Scanlon P, et al. Screening for diabetic retinopathy: new perspectives and challenges. Rev Lancet Diabetes Endocrinol 2020;8(4):337–84.
- 7. Lin KY, Hsih WH, Lin YB, Wen CY, Chang TJ. Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy. J Diabetes Investig. 2020;12(8):1322–5.
- 8. Skol AD, Jung SC, Sokovic AM, Chen S, Fazal S, Sosina O, et al. Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes. Elife 2020;9:1–20.
- 9. Gajewska B, Śliwińska-Mossoń M. Association of MMP-2 and MMP-9 Polymorphisms with Diabetes and Pathogenesis of Diabetic Complications. Int J Mol Sci 2022;23(18):10571.
- 10. Mohammad G, Kowluru RA. Diabetic retinopathy and signaling mechanism for activation of matrix metalloproteinase-9. J Cell Physiol 2012;227(3):1052–61.
- 11. Zhang Z, Wu X, Cai T, Gao W, Zhou X, Zhao J, et al. Matrix Metalloproteinase 9 Gene Promoter (rs 3918242) Mutation Reduces the Risk of Diabetic Microvascular Complications. Int J Environ Res Public Health 2015;12(7):8023–33.
- 12. Singh K, Goyal P, Singh M, Deshmukh S, Upadhyay D, Kant S, et al. Association of functional SNP-1562C>T in MMP9 promoter with proliferative diabetic retinopathy in north Indian type 2 diabetes mellitus patients. J Diabetes Complications 2017;31(12):1648–51.
- 13. Singh K, Agrawal NK, Gupta SK, Singh K. A Functional Single Nucleotide Polymorphism -1562C>T in the Matrix Metalloproteinase-9 Promoter Is Associated With Type 2 Diabetes and Diabetic Foot Ulcers. 2013;12(3):199-204.
- 14. Committee ADAPP. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2022. Diabetes Care 2022;45(S1):S17–38.
- 15. Saravani S, Yari D, Saravani R, Ahmadabadi CA. Association of COL4A3 (rs55703767), MMP-9 (rs17576) and TIMP-1 (rs6609533) gene polymorphisms with susceptibility to type 2 diabetes. Biomed Reports 2017;6(3):329–34.
- 16. Feng S, Ye G, Bai S, Wei H, Liao X, Li L. Matrix Metalloproteinase-9 −1562C/T Gene Polymorphism Is Associated with Diabetic Nephropathy. Biomed Res Int 2016;2016:1627143.
- 17. Shalaby K, Bahriz R , Mahsoub MME-A N, Said GE. Matrix metalloproteinase-9 gene polymorphism (-1562 C/T) and its correlation with diabetic nephropathy. Egypt J Intern Med. 2021;33:7.
- 18. Singh K, Agrawal NK, Gupta SK, Mohan G, Chaturvedi S, Singh K. Differential Expression of Matrix Metalloproteinase-9 Gene in Wounds of Type 2 Diabetes Mellitus Cases With Susceptible -1562C>T Genotypes and Wound Severity. Int J Low Extrem Wounds 2014;13(2):94–102.
- 19. Beránek M, Kolar P, Tschoplova S, Kankova K, Vasku A. Genetic variations and plasma levels of gelatinase A (matrix metalloproteinase-2) and gelatinase B (matrix metalloproteinase-9) in proliferative diabetic retinopathy. Mol Vis 2008;14:1114–21.
MMP9 −1562 C/T POLİMORFİZMİ, TÜRK TİP 2 DİABETES MELLİTUS HASTALARINDA ARTMIŞ DİYABETİK RETİNOPATİ RİSKİ İLE İLİŞKİLİDİR
Öz
Amaç
Tip 2 diabetes mellitus (T2DM) ve diyabetin mikrokomplikasyonlarından
olan diyabetik retinopati (DR)
gelişimi genetik faktörlerden etkilenmektedir. Matriks
metalloproteinazlar (MMPs), ekstraselüler matriks
proteinlerinin yeniden şekillendirilmesi ve anjiyogenez
gibi pek çok hücresel proseste rol alırlar. Bu çalışmada
Türk toplumunda MMP9 −1562 C/T (rs3918242)
polimorfizmi ile T2DM ve DR gelişim riski arasındaki
ilişkinin araştırılması amaçlanmıştır.
Gereç ve Yöntem
Mevcut çalışmaya 168 DR’si olan T2DM hastası, 168
DR’si olmayan T2DM hastası ve 174 kontrol olmak
üzere toplam 510 birey dahil edilmiştir. Genotipleri belirlemek
amacıyla Polimeraz zincir reaksiyonu-Restriksiyon
fragment uzunluk polimorfizmi (PCR-RFLP)
yöntemi kullanılmıştır.
Bulgular
T2DM gelişimi ile MMP9 −1562 C/T polimorfizmi arasında
bir ilişkiye rastlanmazken, CT ve CT+TT genotipleri
ile T (p=0,001) alleli artmış DR riski ile ilişkili bulunmuştur.
Ayrıca CT (p=0,010) ve CT+TT (p=0,015)
genotip sıklığı proliferatif diyabetik retinopati (PDR)
hastalarında proliferatif olmayan diyabetik retinopati
(NPDR) hastalarına kıyasla yüksek bulunmuş, fakat
regresyon analizi sonrasında sadece insülin kullanımının
(p=0,003) PDR gelişimi ile ilişkili olduğu belirlenmiştir.
Sonuç
Elde ettiğimiz veriler Türk T2DM hastalarında MMP9
−1562 C/T polimorfizminin DR gelişimi ile ilişkili olduğunu,
fakat bu polimorfizm ile DR şiddeti ve T2DM
gelişimi arasında anlamlı bir ilişki bulunmadığını göstermektedir.
Anahtar Kelimeler
Diabetik retinopati MMP9 Polimorfizm Proliferatif diyabetik retinopati Tip 2 diabetes mellitus
Kaynakça
- 1. Simó-Servat O, Hernández C, Simó R. Diabetic Retinopathy in the Context of Patients with Diabetes. Ophthalmic Res 2019;62(4):211–7.
- 2. Han J, Lando L, Skowronska-Krawczyk D, Chao DL. Genetics of Diabetic Retinopathy. Curr Diab Rep. 2019;19(9):67.
- 3. Kowluru RA, Mishra M. Regulation of Matrix Metalloproteinase in the Pathogenesis of Diabetic Retinopathy. Prog Mol Biol Transl Sci 2017;148:67–85.
- 4. Bhatwadekar AD, Shughoury A, Belamkar A, Ciulla TA. Genetics of Diabetic Retinopathy, a Leading Cause of Irreversible Blindness in the Industrialized World. Genes (Basel) 2021;12(8):1200.
- 5. Browning DJ, Stewart MW, Lee C. Diabetic macular edema: Evidence-based management. Indian J Ophthalmol 2018;66(12):1736.
- 6. Simó R, Vujosevic S, Aldington SJ, Silva P, Hernández C, Scanlon P, et al. Screening for diabetic retinopathy: new perspectives and challenges. Rev Lancet Diabetes Endocrinol 2020;8(4):337–84.
- 7. Lin KY, Hsih WH, Lin YB, Wen CY, Chang TJ. Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy. J Diabetes Investig. 2020;12(8):1322–5.
- 8. Skol AD, Jung SC, Sokovic AM, Chen S, Fazal S, Sosina O, et al. Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes. Elife 2020;9:1–20.
- 9. Gajewska B, Śliwińska-Mossoń M. Association of MMP-2 and MMP-9 Polymorphisms with Diabetes and Pathogenesis of Diabetic Complications. Int J Mol Sci 2022;23(18):10571.
- 10. Mohammad G, Kowluru RA. Diabetic retinopathy and signaling mechanism for activation of matrix metalloproteinase-9. J Cell Physiol 2012;227(3):1052–61.
- 11. Zhang Z, Wu X, Cai T, Gao W, Zhou X, Zhao J, et al. Matrix Metalloproteinase 9 Gene Promoter (rs 3918242) Mutation Reduces the Risk of Diabetic Microvascular Complications. Int J Environ Res Public Health 2015;12(7):8023–33.
- 12. Singh K, Goyal P, Singh M, Deshmukh S, Upadhyay D, Kant S, et al. Association of functional SNP-1562C>T in MMP9 promoter with proliferative diabetic retinopathy in north Indian type 2 diabetes mellitus patients. J Diabetes Complications 2017;31(12):1648–51.
- 13. Singh K, Agrawal NK, Gupta SK, Singh K. A Functional Single Nucleotide Polymorphism -1562C>T in the Matrix Metalloproteinase-9 Promoter Is Associated With Type 2 Diabetes and Diabetic Foot Ulcers. 2013;12(3):199-204.
- 14. Committee ADAPP. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2022. Diabetes Care 2022;45(S1):S17–38.
- 15. Saravani S, Yari D, Saravani R, Ahmadabadi CA. Association of COL4A3 (rs55703767), MMP-9 (rs17576) and TIMP-1 (rs6609533) gene polymorphisms with susceptibility to type 2 diabetes. Biomed Reports 2017;6(3):329–34.
- 16. Feng S, Ye G, Bai S, Wei H, Liao X, Li L. Matrix Metalloproteinase-9 −1562C/T Gene Polymorphism Is Associated with Diabetic Nephropathy. Biomed Res Int 2016;2016:1627143.
- 17. Shalaby K, Bahriz R , Mahsoub MME-A N, Said GE. Matrix metalloproteinase-9 gene polymorphism (-1562 C/T) and its correlation with diabetic nephropathy. Egypt J Intern Med. 2021;33:7.
- 18. Singh K, Agrawal NK, Gupta SK, Mohan G, Chaturvedi S, Singh K. Differential Expression of Matrix Metalloproteinase-9 Gene in Wounds of Type 2 Diabetes Mellitus Cases With Susceptible -1562C>T Genotypes and Wound Severity. Int J Low Extrem Wounds 2014;13(2):94–102.
- 19. Beránek M, Kolar P, Tschoplova S, Kankova K, Vasku A. Genetic variations and plasma levels of gelatinase A (matrix metalloproteinase-2) and gelatinase B (matrix metalloproteinase-9) in proliferative diabetic retinopathy. Mol Vis 2008;14:1114–21.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 22 Haziran 2023 |
| Gönderilme Tarihi | 23 Mart 2023 |
| Kabul Tarihi | 29 Mayıs 2023 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 30 Sayı: 2 |
Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi/Medical Journal of Süleyman Demirel University is licensed under Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International.