Genetic variations and plasma levels of gelatinase A (matrix metalloproteinase-2) and gelatinase B (matrix metalloproteinase-9) in proliferative diabetic retinopathy.
OBJECTIVE
Matrix metalloproteinases (MMPs) are postulated to be involved in the development of retinal angiogenesis through the regulation of extracellular matrix. The objective of the present study was to test for a possible association of five single nucleotide polymorphisms (SNPs) in the MMP-2 gene and two polymorphisms in the MMP-9 gene with proliferative diabetic retinopathy (PDR) and to determine their plasma levels.


METHODS
The study comprised 490 Caucasian participants, who were divided into three groups: diabetics with PDR, diabetics without PDR, and nondiabetics. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies determined. Plasma levels of MMP-2 and MMP-9 proteins were analyzed by ELISA.


RESULTS
Neither MMP-2 SNPs nor MMP-9 SNPs revealed significant association with PDR in single-locus comparisons; similarly, MMP-2 haplotype frequencies did not differ notably between groups, although the C-allele of the -1306C/T polymorphism and the C-allele containing haplotype (CGCG) in MMP-2 exhibited marginally significant association with PDR in males (p<0.05, p(corr)=NS). Both MMP-2 and MMP-9 plasma levels showed statistically significant differences among the studied groups (p<0.001 and p=0.001, respectively) with highest levels in the PDR group. MMP-2 plasma levels were markedly higher in carriers of either the -1306CC and -1306CT genotypes and (p=0.009) or CGCG haplotype (p=0.043).


CONCLUSIONS
These findings indicate that genotype- and haplotype-specific effects on MMP-2 expression corresponding with its plasma levels may contribute to the susceptibility to PDR.
Beránek
Michal
M
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. mberanek@med.muni.cz
Kolar
Petr
P
Tschoplova
Svatava
S
Kankova
Katerina
K
Vasku
Anna
A
D000328:Adult; D000368:Aged; D003930:Diabetic Retinopathy / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D012727:Sex Characteristics
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9