Endocrine Abstracts

Aims: Few studies investigated the association of genetic difference in metalloproteinase-2 (MMP-2) gene with diabetic retinopathy but with mixed outcome. The aim of the study is to investigate the association between a set of MMP-2 genetic variants and the risk of diabetic retinopathy in an Arab Tunisian population with type 2 diabetes.

Subjects and Methods: A retrospective case-control study involving 779 type 2 diabetes patients with or without diabetic retinopathy was conducted. A total of four MMP-2 SNPs (rs243865 (C/T), rs243864 (T/G), rs243866 (G/T) and rs2285053 (C/T)) were selected for this study, based on their established MAF (>5%) in Caucasians, and association with DR. Genotyping of MMP-2 variants was performed by real time PCR. Replicated blinded quality control samples were included to evaluate reproducibility of the genotyping procedure; concordance was >99%.

Results: The minor allele frequency (MAF) of the rs243864 MMP-2 variant was significantly higher among diabetic retinopathy patients. Setting homozygous wild type genotype carrier as reference, the rs243864T/G allele was associated with increased risk of diabetic retinopathy under the dominant, recessive, and additive models which persisted when key covariates were controlled for, while a reduced risk of diabetic retinopathy progression was seen after adjustment between non-proliferative and proliferative diabetic patients. Furthermore, the heterozygous genotype GT of the rs243866 variant is positively associated with the risk of proliferative diabetic retinopathy in the additive model. A limited linkage disequilibrium (LD) was revealed between the four-matrix metalloproteinase-2 variants. Four-loci haplotype analysis identified GCTC, TTTC, and GCTT haplotypes to be positively associated with the risk of diabetic retinopathy.

Conclusion: MMP-2 constitutes an at-risk locus of risk of DR, and for the first time, we found an association in an Arab Tunisian population where the MMP-2 gene variant rs243864 (–790T/G) and rs243866 (-1575G/T) are linked with the risk of DR development and progression.