ABSTRACT
Diabetic retinopathy (DR) is a complication of diabetes mellitus that can lead to vision loss and blindness. It is driven by various biochemical processes and molecular mechanisms, including lipid peroxidation and disrupted aldehyde metabolism, which contributes to retinal tissue damage and the progression of the disease. The elimination and processing of aldehydes in the retina rely on the crucial role played by aldehyde dehydrogenase (ALDH) and aldo-keto reductase (AKR) enzymes. This review article investigates the impact of oxidative stress, lipid-derived aldehydes, and advanced lipoxidation end products (ALEs) on the advancement of DR. It also provides an overview of the ALDH and AKR enzymes expressed in the retina, emphasizing their growing importance in DR. Understanding the relationship between aldehyde metabolism and DR could guide innovative therapeutic strategies to protect the retina and preserve vision in diabetic patients. This review, therefore, also explores various approaches, such as gene therapy and pharmacological compounds that have the potential to augment the expression and activity of ALDH and AKR enzymes, underscoring their potential as effective treatment options for DR.
ABSTRACT
BACKGROUND: CDKN1A gene encoding p21 is an important tumour supressor involved in the pathogenesis of cancers. A few studies have been devoted to the association between CDKN1A single nucleotide polymorphisms (SNPs) and esophageal cancer (EC) in China, India and Iran. The aim of this case-control study was to investigate the association of CDKN1A polymorphisms with EC risk in the Turkey population for the first time. METHODS: In the present study, CDKN1A SNPs (rs1801270 C > T, rs1059234 C > A and rs3176352 C > G) were genotyped with the use of TaqMan SNP genotyping assays in 102 patients and 119 controls. RESULTS: The genotypes and alleles of CDKN1A SNPs were not significantly different among patients and controls. However, TT-genotype and T-allele of the rs1059234, the rs1801270 CC-genotype and rs3176352 G-allele were significantly associated with EC risk for ≤ 55 age (p < 0.05). In those over 55 age, CC-genotype and C-allele of the rs1059234 was significantly associated with EC (p < 0.05). The rs1059234 T-carriers had a higher risk of high globulin level (p = 0.017) and low albumin/globulin ratio (p = 0.019) when compared to non-T carriers (CC). The rs3176352 CC-genotype carriers had a higher risk of esophageal adenocarcinoma (EAC) subtype when compared to CG-genotype carriers and CG-genotype carriers had a higher risk of squamous cell carcinoma (ESCC) subtype (OR/95% CI = 4.00/1.06-15.08, p = 0.04). The rs3176352 CC-genotype is also a risk factor for the higher BMI (p = 0.04) and the higher CA-19-9 level (p = 0.009). CONCLUSION: Our study suggests that the CDKN1A polymorphisms may play an important role in EC risk in relation to age. Future studies are needed to validate our findings.
