Amanda Crawford

Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease

The presence and progression of numerous diseases have been linked to deficiencies in antioxidant systems. The relationships between single nucleotide polymorphisms (SNPs) arising from specific antioxidant enzymes and diseases associated with elevated oxidative stress have been studied with the rationale that they may be useful in screening for diseases. The purpose of this narrative review is to analyse evidence from these studies. The antioxidant enzyme SNPs selected for analysis are based on those most frequently investigated in relation to diseases in humans: superoxide dismutase (SOD2) Ala16Val (80 studies), glutathione peroxidise (GPx1) Pro197Leu (24 studies) and catalase C-262T (22 studies). Although the majority of evidence supports associations between the SOD2 Ala16Val SNP and diseases such as breast, prostate and lung cancers, diabetes and cardiovascular disease, the presence of the SOD2 Ala16Val SNP confers only a small, clinically insignificant reduction (if any) in the risk of these diseases. Other diseases such as bladder cancer, liver disease, nervous system pathologies and asthma have not been consistently related to this SOD SNP genotype. The GPx1 Pro197Leu and catalase C-262T SNP genotypes have been associated with breast cancer, but only in a small number of studies. Thus, currently available evidence suggests antioxidant enzyme SNP genotypes are not useful for screening for diseases in humans.

Glutathione peroxidase, superoxide dismutase and catalase genotypes and activities and the progression of chronic kidney disease

BACKGROUND Oxidative stress has been linked to the progression of disease, including chronic kidney disease (CKD). The aim of the present study was to determine the association between single-nucleotide polymorphisms (SNPs) of the antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase and their activities and the progression of CKD. METHODS This is a prospective cohort study of 185 CKD patients (Stages 2-4), followed for up to 12 months. All patients were genotyped for SNPs of SOD (SOD Ala16Val), GPx (GPx Pro197Leu) and catalase (C-262T). The rate of change over the study period of estimated glomerular filtration rate (eGFR), plasma and red blood cell (RBC) GPx, RBC SOD and RBC catalase activities were determined. RESULTS CKD patients with the SOD Ala/Val and Val/Val genotypes had a significantly greater eGFR decline compared to those with the Ala/Ala genotype (Ala/Val compared with Ala/Ala odds ratio (OR) 0.35, 95% CI 0.19 to 0.64, P = 0.001; Val/Val compared with Ala/Ala OR 0.25, 95% CI 0.10 to 0.65, P = 0.005). The progression of CKD was not associated with SNPs of the GPx or catalase genes studied but there was a direct relationship between the rate of change of plasma GPx activity and the rate of change of eGFR over 12 months (P = 0.025). CONCLUSION CKD patients with the SOD Ala/Val and Val/Val genotypes have a greater decline in kidney function than those with the Ala/Ala genotype.

Relationship between antioxidant enzyme genotype and activity and kidney function: a case-control study

BACKGROUND Oxidative stress is associated with the progression of chronic kidney disease (CKD). Links between antioxidant enzyme SNPs such as superoxide dismutase (SOD) Ala16Val, glutathione peroxidase (GPx) Pro197Leu and catalase C- 262T and CKD have not been investigated. This study compared antioxidant genotypes and activities of CKD patients with population controls, and determined their relationship to kidney function. METHODS CKD patients (n = 230) and controls (n = 224) were screened for the GPx, SOD and catalase SNPs. Plasma and red blood cell (RBC) GPx, RBC SOD and RBC catalase activities, and estimated glomerular filtration rate (eGFR) were measured. RESULTS Significantly more CKD patients (n = 5) had the GPx Leu/Leu genotype compared to controls (n = 0), and had lower eGFR (p = 0.054). CKD patients had significantly lower plasma GPx and RBC catalase activities compared to controls, whereas RBC GPx and RBC SOD activities were significantly higher in CKD patients (p < 0.001). CONCLUSIONS CKD is associated with reduced plasma GPx and catalase activities and enhanced RBC GPx and SOD activities. Although, genotype frequencies were similar for both groups, lower eGFR was associated with the GPx Leu/ Leu genotype.

Tachykinin (NK1, NK2 and NK3) receptor, transient receptor potential vanilloid 1 (TRPV1) and early transcription factor, cFOS, mRNA expression in rat tissues following systemic capsaicin treatment.

Capsaicin, the pungent component of chilli pepper, stimulates TRPV1-expressing cells which are followed by desensitisation to subsequent exposure to capsaicin and other TRPV1 activators. At high systemic doses (>125 mg/kg), capsaicin produces long-term changes in both tachykinin receptor and TRPV1 expression and function in rats. However, whether desensitising (low) doses of capsaicin (~50 mg/kg) affect tachykinin receptor and TRPV1 gene expression in the short term has yet to be investigated. The aim of the present study was to compare tachykinin receptor (NK1, NK2 and NK3) and TRPV1 mRNA expression 24h after administration of capsaicin (50 mg/kgs.c.). Tachykinin receptor and TRPV1 mRNA were detected in all tissues studied with expression levels differing by up to 2500-fold between tissues. The highest expression of TRPV1 and NK1 mRNA was observed in the salivary gland, whereas NK2 mRNA expression was highest in the urinary bladder and NK3 mRNA expression in the frontal cortex. In the cervical spinal cord of rats treated with capsaicin, NK1 and NK3 mRNA expression were reduced by 56% and 80%, respectively (P<0.05), whereas NK2 and TRPV1 mRNA expression were increased 2.2- and 1.4-fold, respectively (P<0.05). NK1 and NK2 mRNA expression were decreased (P<0.05) in the urinary bladder and gastric fundus, respectively, following capsaicin treatment. There was a marked 100-fold increase in cFOS mRNA expression and 100-fold decrease in NK2 mRNA expression in the whole blood of capsaicin-treated rats. In conclusion, these studies show that tachykinin receptor and TRPV1 mRNA expression undergo significant changes within 24h of systemic low-dose capsaicin administration.