Association of functional SNP-1562C &gt; T in MMP9 promoter with proliferative diabetic retinopathy in north Indian type 2 diabetes mellitus patients

Singh, Kanhaiya; Goyal, Pankaj; Singh, Manju; Deshmukh, Sujit; Upadhyay, Divyesh; Kant, Shri; Agrawal, N K; Gupta, Sanjeev Kumar; Singh, Kiran

doi:10.1016/j.jdiacomp.2017.08.010

Cited by 13 publications

(9 citation statements)

References 17 publications

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“…There are very few studies in the literature investigating the association between MMP9 polymorphisms and type 2 diabetes mellitus (T2DM) and DR. In these studies, it was reported that −1562 C/T variation may be related with susceptibility to these diseases (12,13). A similar study was not found in the Turkish population.…”

Section: Introductionmentioning

confidence: 83%

Mmp9 −1562 C/T Poli̇morfi̇zmi̇, Türk Ti̇p 2 Di̇abetes Melli̇tus Hastalarinda Artmiş Di̇yabeti̇k Reti̇nopati̇ Ri̇ski̇ İle İli̇şki̇li̇di̇r

İçduygu

Akgün

Alp

et al. 2023

SDÜ Tıp Fakültesi Dergisi

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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 Methods: 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 non-proliferative 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.

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Section: Introductionmentioning

confidence: 83%

Mmp9 −1562 C/T Poli̇morfi̇zmi̇, Türk Ti̇p 2 Di̇abetes Melli̇tus Hastalarinda Artmiş Di̇yabeti̇k Reti̇nopati̇ Ri̇ski̇ İle İli̇şki̇li̇di̇r

İçduygu

Akgün

Alp

et al. 2023

SDÜ Tıp Fakültesi Dergisi

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“…Regarding DR and a possible genetic background, Singh K. et al postulated that the functional SNP -1562C>T in the promoter of the MMP-9 gene plays a very important role in developing proliferative DR due to the elevated MMP-9 production from the high expressing T allele leading to retinal angiogenesis [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the pathogenesis of DR, activated MMPs cause the damage of mitochondria and augment retinal capillary cell apoptosis [ 19 ]. Only a few studies regarding the MMPs gene single nucleotide polymorphism (SNP) studies have been completed, and the results of their correlation with DR are conflicting [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinase-2 (MMP-2 ) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients

Andjelic

Radojković

Nikolić

et al. 2022

Balkan Journal of Medical Genetics

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Vascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases MMP-2 and MMP-9, zinc-dependent endopeptidases through remodeling of the extracellular matrix, can contribute to the onset and progression of diabetic vascular complications. The aim of our study was to assess whether there is a major difference in single nucleotide polymorphisms in the MMP-2 (at position -1306C˃T) and MMP-9 (at position -1562C˃T) gene in type 2 diabetic patients and healthy controls and to determine whether there is an association of these gene variants with the presence of microvascular complications in diabetic patients. Our study included 102 type 2 diabetes patients and a control group which was comprised of 56 healthy controls. All diabetic patients were screened for microvascular diabetes complications. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies were determined. The MMP-2 variant -1306C>T showed a negative correlation with type 2 diabetes (p=0.028). It was also shown that the presence of the -1306C allele increases the probability of developing type 2 diabetes. This was a 2.2 fold increase and that the -1306 T allele has a protective role in regards to type 2 diabetes. The MMP-2 variant -1306T showed a negative correlation with diabetic polyneuropathy (p=0.017), meaning that allele-1306T has a protective role in regards to diabetic polyneuropathy while the presence of allele -1306C increases the probability of developing diabetic polyneuropathy by 3.4 fold. Our study showed that the MMP-2 gene variant (-1306C) doubles the risk of developing type 2 diabetes, and for the first time an association of this gene variant and the presence of diabetic polyneuropathy was shown.

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“…Matrix metalloproteinases (MMPs) are important proteases involved in connective tissue remodeling and ECM degradation [ 28 ] and play important roles in various developmental processes, such as morphogenesis, angiogenesis, and vascular remodeling. Among the MMPs, those with gelatinase activity (MMP9 and MMP2) have shown a clear dual role in the development of DR.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-based Investigation of the Underlying Mechanism of Panax notoginseng Treatment of Diabetic Retinopathy

Piao

Sun

Jin

et al. 2020

CCHTS

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Background: Panax notoginseng, a Chinese herbal medicine, has been widely used to treat vascular diseases. Diabetic retinopathy (DR) is one of the complications of diabetic microangiopathy. According to recent studies, the application of Panax notoginseng extract and related Chinese patent medicine preparations can significantly improve DR. However, the pharmacological mechanisms remain unclear. Therefore, the purpose of this study was to decipher the potential mechanism of Panax notoginseng treatment of DR using network pharmacology. Methods: We evaluated and screened the active compounds of Panax notoginseng using the Traditional Chinese Medicine Systems Pharmacology database and collected potential targets of the compounds by target fishing. A multi-source database was also used to organize targets of DR. The potential targets as the treatment of DR with Panax notoginseng were then obtained by matching the compound targets with the DR targets. Using protein-protein interaction networks and topological analysis, interactions between potential targets were identified. In addition, we also performed gene ontology-biological process and pathway enrichment analysis for the potential targets by using the Biological Information Annotation Database. Results: Eight active ingredients of Panax notoginseng and 31 potential targets for the treatment of DR were identified. The screening and enrichment analysis revealed that the treatment of DR using Panax notoginseng primarily involved 28 biological processes and 10 related pathways. Further analyses indicated that angiogenesis, inflammatory reactions, and apoptosis may be the main processes involved in the treatment of DR with Panax notoginseng. In addition, we determined that the mechanism of intervention of Panax notoginseng in treating DR may involve five core targets, VEGFA, MMP-9, MMP-2, FGF2, and COX-2. Conclusion: Panax notoginseng may treat diabetic retinopathy through the mechanism of network pharmacological analysis. The underlying molecular mechanisms were closely related to the intervention of angiogenesis, inflammation, and apoptosis with VEGFA, MMP-9, MMP-2, FGF2, and COX-2 being possible targets.

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Association of functional SNP-1562C > T in MMP9 promoter with proliferative diabetic retinopathy in north Indian type 2 diabetes mellitus patients

Cited by 13 publications

References 17 publications

Mmp9 −1562 C/T Poli̇morfi̇zmi̇, Türk Ti̇p 2 Di̇abetes Melli̇tus Hastalarinda Artmiş Di̇yabeti̇k Reti̇nopati̇ Ri̇ski̇ İle İli̇şki̇li̇di̇r

Mmp9 −1562 C/T Poli̇morfi̇zmi̇, Türk Ti̇p 2 Di̇abetes Melli̇tus Hastalarinda Artmiş Di̇yabeti̇k Reti̇nopati̇ Ri̇ski̇ İle İli̇şki̇li̇di̇r

Matrix metalloproteinase-2 (MMP-2 ) and-9 (MMP-9) gene variants and microvascular complications in type 2 diabetes patients

Network Pharmacology-based Investigation of the Underlying Mechanism of Panax notoginseng Treatment of Diabetic Retinopathy

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