Gene polymorphisms of the MMP1, MMP9, MMP12, IL-1β and TIMP1 and the risk of primary open-angle glaucoma


Jacek P. Szaflik
Department of Ophthalmology
Medical University of Warsaw
SPKSO University Hospital
ul. Sierakowskiego 13
03-709 Warszawa


Background:  Primary open-angle glaucoma (POAG) is the main cause of irreversible blindness worldwide. Matrix metalloproteinases (MMPs) and their regulators (TIMPs and ILs) have been extensively studied as POAG risk factors. Recent reports have showed several single-nucleotide polymorphisms (SNPs) for MMPs, TIMPs and ILs encoding genes in patients with POAG. The aim of this study was to investigate association of the -1607 1G/2G MMP1, -the 1562 C/T MMP9, the -82 A/G MMP12, the -511 C/T IL-1β and the 372 T/C TIMP1 gene polymorphisms with POAG occurrence and to investigate their impact on main clinical features.

Material and methods:  In the present case–control study, we examined group of 511 unrelated Caucasian subjects consist of 255 patients with POAG (mean age 70 ± 15) and 256 controls (mean age 67 ± 16). Determination of genes polymorphic variants was made using polymerase chain reaction–restriction fragment length polymorphism technique (PCR-RFLP). The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated.

Results:  Presented study showed statistically significant increase in the POAG development risk of the -1607 2G/2G MMP1 genotype (OR 1.75; 95% CI, 1.11–2.75; p = 0.014) and for the -1607 2G MMP1 allele (OR 1.35; 95% CI, 1.05–1.73; p = 0.017), as well as for the -1562 C/T MMP9 genotype (OR 1.74; 95% CI, 1.17–2.59; p = 0.006) and the -1562 T MMP9 allele (OR 1.55; 95% CI, 1.10–2.17; p = 0.012) in patients with POAG in comparison with healthy control group. We also observed positive association of the -511 T/T IL-1β genotype (OR 2.60; 95% CI, 1.41–4.80; p = 0.002) as well as the -511 T IL-1β allele occurrence with an increased POAG development risk (OR 1.47; 95% CI, 1.13–1.90; p = 0.003). Furthermore, we found an association of the -1607 1G/2G MMP1, -1562 C/T MMP9 (anova, p < 0.001) and the -511 C/T IL-1β gene polymorphism (anova, p < 0.05) with decreased retinal nerve fibre layer (RNFL) thickness in patients with POAG group. Results displayed also an association of the 372 T/C TIMP1 gene polymorphism with normal range RNFL (anova, p < 0.001). We observed an association of decreased RA value (rim area) with the -82 A/G MMP12 (anova, p < 0.001). Normal RA value was observed in patients with POAG group connected with the 372 T/C TIMP1 (anova, p < 0.05) and the -511 C/T IL-1β (anova, p < 0.05) genes polymorphisms occurrence. Finally, results showed an association of the -1562 C/T MMP9 (anova, p < 0.001) gene polymorphism with decreased cup/disc index in patients with POAG group.

Conclusion:  In conclusion, we suggest that the -1607 1G/2G MMP1, -1562 C/T MMP9, -511 C/T IL-1β gene polymorphisms can be considered as an important risk factors associated with POAG.