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01 July 2011

Association of MMP1-1607 1G/2G and TIMP1 372 T/C gene polymorphisms with risk of primary open angle glaucoma in a Polish population

Ireneusz MajsterekACDEFG, Lukasz MarkiewiczBCD, Karolina PrzybylowskaBCDEF, Mira GacekBCDF, Anna K. KurowskaBC, Anna KaminskaBCF, Jerzy SzaflikADG, Jacek P. SzaflikABDEFG

DOI: 10.12659/MSM.881854

Med Sci Monit 2011; 17(7): CR417-421

Abstract

Background: Primary open angle glaucoma (POAG) is considered to be a leading cause of irreversible blindness worldwide. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) have been extensively studied as POAG risk factors. Recently, several single-nucleotide polymorphisms (SNPs) for MMPs and TIMPs encoding genes have been reported in POAG patients. The aim of this study was to investigate association of the -1607 1G/2G MMP1 and 372 T/C TIMP1 gene polymorphisms with risk of POAG in a Polish population.
Material/Methods: In the present case-control study we examined a group of 449 unrelated Caucasian subjects consisting of 196 POAG patients (66 males and 130 females; mean age 70±14) and 253 controls (72 males and 181 females; mean age 67±16). The MMP1-1607 1G/2G and TIMP1 372 T/C gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated.
Results: We found a statistically significant increase of the 2G/2G genotype (OR 1.73; 95% CI 1.05–2.86; p=0.019) as well as the 2G allele frequency (OR 1.34; 95% CI 1.03–1.75; p=0.017) of MMP1 in POAG patients in comparison to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the TIMP1 polymorphism between patients and controls group. We also did not find any association of TIMP1 with MMP1 gene-gene interaction and risk of POAG occurrence.
Conclusions: In conclusion, we suggest that the -1607 1G/2G polymorphism of MMP1 gene may be considered as an important risk factor associated with primary open angle glaucoma in a Polish population. However, further in vivo study is needed to evaluate biological importance of MMPs polymorphisms as a risk factor of POAG.

Keywords: Matrix Metalloproteinase 1 - genetics, Glaucoma, Open-Angle - genetics, Genome-Wide Association Study, Genetic Predisposition to Disease - genetics, Gene Frequency, DNA Primers - genetics, Aged, 80 and over, Poland, Polymorphism, Single Nucleotide - genetics, Tissue Inhibitor of Metalloproteinase-1 - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750