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A polymorphism in the gene encoding carnosinase (CNDP1) as a predictor of mortality and progression from nephropathy to end-stage renal disease in type 1 diabetes mellitus |
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| Authors: | A Alkhalaf S J L Bakker H J G Bilo R O B Gans G J Navis D Postmus C Forsblom P H Groop N Vionnet S Hadjadj M Marre H H Parving P Rossing L Tarnow |
| Institution: | 1. Department of Internal Medicine, University Medical Center Groningen, Hanzeplein 1, P.O. Box?30.001, 9700, RB, Groningen, The Netherlands 2. Diabetes Center, Isala Clinics, Zwolle, the Netherlands 3. Department of Epidemiology, University Medical Center Groningen, Groningen, the Netherlands 4. Folkh?lsan Institute of Genetics, Folkh?lsan Research Center, Biomedicum Helsinki, Helsinki, Finland 5. Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland 6. Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé (UMRS) 937, Pierre and Marie Curie University, Paris, France 7. Department of Endocrinology and Diabetology, Centre Hospitalier Universitaire Poitiers, Poitiers, France 8. INSERM, Unit 927 and CIC802, Poitiers, France 10. INSERM Unit 695, University of Paris, Paris, France 9. Department of Endocrinology, Diabetology and Nutrition, Bichat-Claude Bernard University Hospital, Paris, France 11. Department of Medical Endocrinology, University of Copenhagen, Copenhagen, Denmark 12. Faculty of Health Science, Aarhus University, Aarhus, Denmark 13. Steno Diabetes Center, Gentofte, Denmark |
| Abstract: | Aims/hypothesisHomozygosity for a five leucine repeat (5L–5L) in the carnosinase gene (CNDP1) has been found to be cross-sectionally associated with a low frequency of diabetic nephropathy (DN), mainly in type 2 diabetes. We prospectively investigated in patients with type 1 diabetes whether: (1) 5L–5L is associated with mortality; (2) there is an interaction of 5L–5L with DN or sex for prediction of mortality; and (3) 5L–5L is associated with progression to end-stage renal disease (ESRD).MethodsIn this prospective study in white European patients with type 1 diabetes, individuals with DN were defined by persistent albuminuria ≥300 mg/24 h. Controls without nephropathy were defined by persistent (>15 years) normoalbuminuria <30 mg/24 h. Leucine repeats were assessed with a fluorescent DNA analysis system. Onset of ESRD was defined by need to start chronic dialysis or kidney transplantation.ResultsThe study involved 916 patients with DN and 1,170 controls. During follow-up for 8.8 years, 107 patients (14%) with 5L–5L died compared with 182 patients (13.8%) with other genotypes (p?=?0.99). There was no significant interaction of 5L–5L with DN for prediction of mortality (p?=?0.57), but a trend towards interaction with sex (p?=?0.08). In patients with DN, HR for ESRD in 5L–5L vs other genotypes was not constant over time, with increased risk for 5L–5L beyond 8 years of follow-up (p?=?0.03).Conclusions/interpretationCNDP1 polymorphism was not associated with mortality, and nor was there an interaction of this polymorphism with DN for prediction of mortality in patients with type 1 diabetes. CNDP1 polymorphism predicts progression to ESRD in patients with DN, but only late after baseline measurements. |
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