Single-nucleotide polymorphisms in P450 oxidoreductase and peroxisome proliferator-activated receptor-α are associated with the development of new-onset diabetes after transplantation in kidney transplant recipients treated with tacrolimus
| Autor: | Teun van Gelder, Ron H.N. van Schaik, Laure Elens, Dennis A. Hesselink, Ferdi Sombogaard |
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| Přispěvatelé: | Clinical Chemistry, Pharmacy, Internal Medicine |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotyping Techniques Peroxisome proliferator-activated receptor Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Tacrolimus Young Adult Diabetes mellitus genetics SDG 3 - Good Health and Well-being Risk Factors Internal medicine Diabetes mellitus Diabetes Mellitus Genetics medicine Humans Genetic Predisposition to Disease PPAR alpha Prospective Studies General Pharmacology Toxicology and Pharmaceutics Molecular Biology Genetics (clinical) Kidney transplantation Aged NADPH-Ferrihemoprotein Reductase chemistry.chemical_classification Genetic Variation Middle Aged medicine.disease Kidney Transplantation Transplantation Endocrinology chemistry Molecular Medicine Female Immunosuppressive Agents Pharmacogenetics |
| Zdroj: | Pharmacogenetics Genomics, 23(12), 649-657. Lippincott Williams & Wilkins |
| ISSN: | 1744-6872 |
| Popis: | BackgroundNew-onset diabetes after transplantation (NODAT) is an important complication after kidney transplantation. The etiology of the malady is multifactorial and includes both environmental and genetic factors. NODAT is a polygenic disease and many single-nucleotide polymorphisms could constitute potential risk factors. Peroxisome proliferator-activated receptor (PPAR) and P450 oxidoreductase (POR) play a central role in the control of energy metabolism in humans. Some recent data highlighted a possible functional impact of two single-nucleotide polymorphisms in PPAR (rs4253728 G>A and rs4823613 A>G) and one coding variant in POR (rs1057868; POR*28; A503V) on the activity of their respective encoded proteins. In the present study, we assessed the association between these variants and the risk of developing NODAT after kidney transplantation.MethodsDevelopment of NODAT was investigated in 101 renal transplant recipients receiving tacrolimus-based immunosuppressive therapy. Patients were genotyped for PPAR and POR. The incidence of NODAT was compared between different genotypes. Kaplan-Meier and Cox's proportional-hazard analysis were used to evaluate the association of NODAT with potential risk factors. Potential nongenetic risk factors were also considered.ResultsThe PPAR rs4253728A>G and POR*28 variant alleles were both independently associated with an increased risk for NODAT with respective odds ratios of 8.6 [95% confidence interval (CI)=1.4-54.2; P=0.02] and 8.1 (95% CI=1.1-58.3; P=0.04). Other risk predictors included sex and body weight.ConclusionThis candidate-gene study shows that polymorphisms in PPAR and POR might predispose patients being treated with tacrolimus to the development of NODAT after kidney transplantation. Patient management after organ transplantation might benefit from genotype data. |
| Databáze: | OpenAIRE |
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