Correlations of TIMP2 and TIMP3 gene polymorphisms with primary open-angle glaucoma

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide.
• The underlying genetic factors and molecular mechanisms of POAG remain incompletely understood.
• Metalloproteinases and their inhibitors play roles in tissue remodeling and extracellular matrix regulation, potentially influencing ocular health.

Purpose of the Study:

• To investigate the association between specific gene polymorphisms of tissue inhibitor of metalloproteinase-2 (TIMP2) and TIMP3 and the risk of developing POAG.
• To explore potential correlations between these genetic variations and clinical/biochemical markers in POAG patients.

Main Methods:

• A case-control study involving 295 POAG patients and 200 healthy controls.
• Collection of demographic data, medical history (hypertension, diabetes, hyperlipemia), and family history.
• Measurement of vascular endothelium and hemorheology indexes, including nitric oxide (NO), endothelin-1 (ET-1), plasma viscosity (PV), hematocrit (HCT), and fibrinogen (FIB).
• Genotyping of TIMP2 rs796391657 and TIMP3 rs8136803 polymorphisms using TaqMan-MGB probe assay.

Main Results:

• POAG patients showed higher prevalence of diabetes, hyperlipemia, and family history compared to controls.
• The POAG group exhibited lower nitric oxide (NO) levels and higher levels of endothelin-1 (ET-1), plasma viscosity (PV), hematocrit (HCT), and fibrinogen (FIB).
• Significant differences in the distribution of genotypes and alleles for TIMP2 rs796391657 (CC and C allele higher) and TIMP3 rs8136803 (GG and G allele higher) were observed between POAG patients and controls.

Conclusions:

• The studied polymorphisms in TIMP2 (rs796391657) and TIMP3 (rs8136803) genes are significantly correlated with primary open-angle glaucoma.
• These genetic variations may contribute to the pathogenesis of POAG, potentially through alterations in vascular and hemorheological parameters.