MATRIX METALLOPROTEINASE-2 (MMP-2 ) AND-9 (MMP-9) GENE VARIANTS AND MICROVASCULAR COMPLICATIONS IN TYPE 2 DIABETES PATIENTS
Andjelic Jelic M٭ˡ, Radojkovic D², Nikolic A², Rakicevic Lj², Babic T², Jelic D³, Lalic NM⁴
*Corresponding Author: Marina Andjelic Jelic, Department of Endocrinology, Diabetes and Metabolic Diseases, Clinical Medical Centre Zvezdara, Dimitrija Tucovica 161, 11000 Belgrade, Serbia, Phone +381 64 122 2010 Fax +381 11 3088733, E mail: drmajelic@gmail.com
page: 6

DISCUSSION

In our study, our primary goal was to assess the possible differences in MMP-2 and MMP-9 gene polymorphism between patients with type 2 diabetes and healthy controls. Our results showed that the presence of the MMP-2 allele -1306C nearly doubles the risk of developing type 2 diabetes mellitus, while the -1306T allele provides protection against this disease. This correlates with the results of Sarray et al., who, for the first time, showed an association of the MMP-2-1306C>T gene variant with the susceptibility to developing type 2 diabetes, therefore confirming the protective effect of the T allele. [35] To our knowledge, this is the first study investigating MMP-2 and MMP-9 genetic variants and all three microvascular complications. 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]. A statistically significant difference was observed in both allele and genotype distributions, but only between patients with proliferative retinopathy versus healthy controls with no DM. There were, however, no significant differences between patients with DM, no matter if they have DR or not. This is the same result as our study. Due to the limited number of patients with proliferative retinopathy we were not able to establish if there is a significant difference between these patients and healthy controls. In another study, Beranek M. et al. showed that plasma levels of MMP-2 were significantly higher in patients with proliferative DR who were carriers of the -1306 CC or the -1306 CT genotypes [21]. In Beranek’s study, no major differences were found among the groups (diabetics with non-proliferative DR, diabetics with proliferative DR, and healthy controls) when comparing the genotype distribution for MMP-2-1306C>T and MMP-9-1562 C>T variants. This is consistent with our results. MMPs are regarded as very important players in the development of diabetic polyneuropathy, not only by caus-ing extracellular matrix abnormalities but also by causing neuronal injury which leads to the development of neuropathic pain. So far, no genetic study has been performed regarding MMP gene variants and the presence of DPN. Our results showed that the presence of the MMP-2 allele -1306C increases the probability of developing diabetic polyneuropathy by a factor of 3.4 times. This can be potentially used as genetic marker for detecting those diabetic patients who are at risk of developing this threatening vascular complication. Of course, we need more extensive studies to confirm this finding. We found no correlation between either MMP-2 or MMP-9 gene variants and diabetic nephropathy. This was probably due to the limited number of patients with this complication in the study group. In conclusion, our study showed that the variant -1306C>T in the MMP-2 gene doubles the risk of developing type 2 diabetes, and we showed, for the first time, an association of this gene variant and the presence of diabetic polyneuropathy. As matrix metalloproteinases play an important role in the development of vascular diabetic complications, future studies with a larger number of patients are needed so as to verify variants in the genes for MMPs as markers for diabetic complications . Declaration of Interest. The authors report no conflict of interest. The authors alone are responsible for the content and writing of this article.



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