RESUMO
BACKGROUND: Keratoconus (KC) is a degenerative eye disease which results from thinning of the cornea and causes vision distortion. Oxidative stress damage to KC corneas may be because of the failure of corneas to process reactive oxygen species which leads to corneal thinning and loss of vision. Genetic variants in antioxidant defense genes such as catalase (CAT) and glutathione peroxidase (GPX) can decrease antioxidant capacity or increase oxidative stress and alter the risk of KC in patients. We investigated and evaluated the effects of single nucleotide polymorphisms in CAT, GPX-1 on the risk of KC in an Iranian population sample. METHODS: This case-control study was performed on 140 patients with KC and 150 healthy control subjects in a sample of Iranian population from Zahedan, southern Iran in 2015. Genotyping of CAT rs7943316 and GPX-1 rs1050450 polymorphisms was done using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: CAT rs7943316 A/T, AA genotype and A allele have a protective role against disease (OR =0.28, 95% CI =0.13-0.61, P=0.001 and OR = 0.50, 95% CI =0.35-0.72, P=0.0001, respectively) and decreased the risk of KC. Moreover, GPX-1 rs1050450 T allele increased the risk of KC in comparison with C allele (OR = 1.42, 95% CI = 1.01-2.03, P=0.03). CONCLUSION: CAT rs7943316 A/T, AA genotype, and A allele decreased the risk of KC. Moreover, in GPX-1 rs1050450 C/T polymorphism, T allele was associated with an increased risk of KC in our population.
RESUMO
Type 2 diabetes (T2D) is defined by high levels of glucose in the blood. The collagen IV level is associated with conditions of hyperglycemia and insulin resistance. Collagen type IV α3 chain (COL4A3) is a structural protein of the extracellular matrix (ECM). Matrix metallopeptidase 9 (MMP-9) is an enzyme that degrades the extracellular matrix and its activity is moderated by TIMP metallopeptidase inhibitor 1 (TIMP-1). The aim of the current study was to examine the association between genetic polymorphisms of COL4A3 (rs55703767), MMP-9 (rs17576) and TIMP-1 (rs6609533) in patients with T2D. This case-control study was performed on 120 Iranian patients with T2D and 120 healthy individuals. Genotypes were analyzed using the amplification refractory mutation system-polymerase chain reaction technique. The findings demonstrated significant differences between genotypic and allelic distributions of COL4A3 (G/T) and MMP-9 (A/G) polymorphisms as follows: COL4A3 (G/T); TT vs. GG, odds ratio (OR)=0.235, 95% confidence interval (CI)=0.063-0.0802 (P=0.013) and T vs. G, OR=0.592, 95% CI=0.371-0.943 (P=0.026); MMP-9 (A/G); AG vs. GG, OR=2.429, 95% CI=1.232-4.820 (P=0.008) and A vs. G, OR=2.176, 95% CI=1.155-4.130 (P=0.013). No significant association was identified between TIMP-1 (A/G) polymorphism and T2D in females and males. Thus, the genotypic and allelic distributions of COL4A3 (G/T) and MMP-9 (A/G) polymorphisms were associated with T2D. In addition, no significant association was identified in the genotypic distribution of the TIMP-1 (A/G) gene in females and in males. Further studies in other ethnic groups are required to confirm these findings.
RESUMO
PURPOSE: Keratoconus (KC) is thinning of the central cornea. Its etiology is unknown, but it may result from degrading of collagen type IV. The major protein in the cornea is collagen. Matrix metalloproteinase-9 (MMP-9) is able to degrade collagen type IV from the basement membrane and extracellular matrix (ECM). MMP-9 enzymatic activity is inhibited by the tissue inhibitor of metalloproteinase-1 (TIMP-1). In the present study, we sought to investigate and evaluate the effects of single nucleotide polymorphisms in COL4A3, MMP-9, and TIMP-1 on the risk of KC in an Iranian population sample. METHODS: This case-control study was performed on 140 KC patients and 150 healthy controls. Genotyping of the COL4A3 rs55703767, MMP-9 rs17576, and TIMP-1 rs6609533 polymorphisms was done using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). RESULTS: Our findings showed that the rs55703767G/T polymorphism decreased the risk of KC (OR = 0.26, 95% CI = 0.08-0.82, P = 0.022). rs17576A/G, associated with KC and the A allele, was significantly overrepresented in healthy individuals. rs6609533A/G (X-chromosome) increased the risk of KC in females (OR = 2.27, 95% CI = 1.06-4.76, P = 0.036). In males, the allele frequency was not associated with KC risk/protection. CONCLUSIONS: This study indicates that in our population, the COL4A3 rs55703767 polymorphism decreased the risk of KC. However, the TIMP-1 rs6609533 polymorphism was associated with an increased risk of KC.
