Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20826743
DOI
10.1093/ndt/gfq550
PII: gfq550
Knihovny.cz E-resources
- MeSH
- Diabetic Nephropathies enzymology genetics mortality MeSH
- Adult MeSH
- Erythrocytes enzymology MeSH
- Genotype MeSH
- Glucose metabolism MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Follow-Up Studies MeSH
- Pentosephosphates metabolism MeSH
- Pentose Phosphate Pathway MeSH
- Cross-Sectional Studies MeSH
- Aged MeSH
- Thiamine metabolism MeSH
- Transaldolase genetics MeSH
- Transketolase genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Glucose MeSH
- Pentosephosphates MeSH
- Thiamine MeSH
- TKTL1 protein, human MeSH Browser
- Transaldolase MeSH
- Transketolase MeSH
BACKGROUND: Pentose phosphate pathway (PPP) represents a potentially 'protective' mechanism in hyperglycaemia due to shunting of glycolytic intermediates into PPP reactions. We hypothesized that thiamine status (plasma and erythrocyte levels of thiamine and its esters) together with genetic variability in key PPP enzymes-transketolase (TKT), transaldolase and TKT-like-might contribute to the progression of diabetic nephropathy (DN) and mortality of diabetics. METHODS: A total of 240 diabetic subjects with variable degree of kidney disease were included at baseline and were followed up for a median of 26 (IQR 21-50) months. Concentrations of thiamine in plasma and whole blood and TKT-catalysed reaction were determined by HPLC. Single-nucleotide polymorphisms (SNPs) (n = 14) were genotyped by means of PCR using TaqMan chemistry (Applied Biosystems, Foster City, CA, USA). RESULTS: Significant differences in pTh, pThDP, eryThDP and eryTKT between DN-stage groups were ascertained (P < 0.05) with advancing stage of DN being accompanied with increasing values of pTh, pThDP and eryTKT but not eryThDP. A highly significant negative correlation (r = - 0.41, P < 0.001) was found between pThDP and eryThDP, and the tertiles of the ratio of eryThDP/pThDP were significantly associated with all-cause mortality rates (P = 0.0072). We also identified significant differences in the rate of DN progression between different pTDP tertile groups (P = 0.0017). No significant genetic effects were found. CONCLUSIONS: The results support the role of 'functional' thiamine deficiency in the development of hyperglycaemia-related pathology. Limited intracellular availability of active TKT co-factor seems to be a dominant abnormality.
References provided by Crossref.org
Association of the IL-6R rs2228145 polymorphism with diabetic nephropathy: A case-control study
Deleterious Effect of Advanced CKD on Glyoxalase System Activity not Limited to Diabetes Aetiology
