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

Abstract

SummaryBackgroundPrimary 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/MethodsIn 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.ResultsWe 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.ConclusionsIn 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.

Gene polymorphisms of theMMP1, MMP9, MMP12, IL-1βandTIMP1and the risk of primary open-angle glaucoma

“…An association of the 2G/2G genotype and 2G allele that we found with POAG occurrence in researched group seems to be in agreement with previously presented studies. Our preliminary results obtained earlier for MMPs polymorphisms have been confirmed (Majsterek et al. 2011).…”

Association of Gene Polymorphisms With Primary Open Angle Glaucoma: A Systematic Review and Meta-Analysis

“…78,79,138,144,148 Significant association was found in the overall populations in allelic (OR 1.33, 95% CI: 1.13-1.57; P ¼ 0.54, I 2 ¼ 0.00), homozygote (OR 1.61, 95% CI: 1.05-2.45; P ¼ 0.53, I 2 ¼ 0.00), heterozygote (OR 1.32, 95% CI: 1.08-1.62; P ¼ 0.95, I 2 ¼ 0.00), and dominant comparisons (OR 1.37, 95% CI: 1.12-1.66; P ¼ 0.80, I 2 ¼ 0.00), but not in the recessive model ( 65,72,77,82,84,85,115 For SNP rs1799750 in the MMP gene, four studies (885 POAG cases and 875 controls) were involved. 94,95,104,121 The pooled results showed that rs1799750 was significantly correlated with POAG in recessive model (OR 1.64, 95% CI: 1.05-2.56; P ¼ 0.01, I 2 ¼ 73. 90).…”

“…SNP 372 T/C in the TIMP1 gene was reported in two studies, involving a total of 451 POAG cases and 509 controls. 94,104 Significant association was found in the overall populations in the recessive model (OR 1.50, 95% CI: 1.12-2.01; P ¼ 0.69, I 2 ¼ 0.00, Table 2, Supplementary Files S11).…”

“…168 Decreased activity of MMPs in the aqueous humor might result in abnormal accumulation of matrix in POAG patients. 169 It was reported that the rs1799750 of the MMP1 gene may be a risk factor associated with POAG in a Polish 94,104 and a Pakistani population. 95 Three hundred seventy-two T/C polymorphisms in tissue inhibitors for metalloproteinases (TIMPs) encoding genes have also been identified in POAG patients.…”

Bibliometric network analysis of glaucoma

“…Recently, several single-nucleotide polymorphisms (SNPs) for MMP-encoding genes have been reported in POAG patients. A statistically significant increase in the occurrence of 2G/2G genotype as well as in 2G allele frequency of MMP1 could be observed in POAG patients compared to healthy controls (Majsterek et al, 2011).…”