The CNDP1 (CTG)5 Polymorphism Is Associated with Biopsy-Proven Diabetic Nephropathy, Time on Hemodialysis, and Diabetes Duration

Author:

Albrecht Thomas1ORCID,Zhang Shiqi12,Braun Jana D.1,Xia Li12,Rodriquez Angelica1,Qiu Jiedong1,Peters Verena3,Schmitt Claus P.3,Born Jacob van den4,Bakker Stephan J. L.4,Lammert Alexander1,Köppel Hannes1,Schnuelle Peter1,Krämer Bernhard K.1,Yard Benito A.1,Hauske Sibylle J.1

Affiliation:

1. Fifth Medical Department (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany

2. Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

3. Centre for Pediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany

4. Nephrology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands

Abstract

Considering that the homozygous CNDP1 (CTG)5 genotype affords protection against diabetic nephropathy (DN) in female patients with type 2 diabetes, this study assessed if this association remains gender-specific when applying clinical inclusion criteria (CIC-DN) or biopsy proof (BP-DN). Additionally, it assessed if the prevalence of the protective genotype changes with diabetes duration and time on hemodialysis and if this occurs in association with serum carnosinase (CN-1) activity. Whereas the distribution of the (CTG)5 homozygous genotype in the no-DN and CIC-DN patients was comparable, a lower frequency was found in the BP-DN patients, particularly in females. We observed a significant trend towards high frequencies of the (CTG)5 homozygous genotype with increased time on dialysis. This was also observed for diabetes duration but only reached significance when both (CTG)5 homo- and heterozygous patients were included. CN-1 activity negatively correlated with time on hemodialysis and was lower in (CTG)5 homozygous patients. The latter remained significant in female subjects after gender stratification. We confirm the association between the CNDP1 genotype and DN to be likely gender-specific. Although our data also suggest that (CTG)5 homozygous patients may have a survival advantage on dialysis and in diabetes, this hypothesis needs to be confirmed in a prospective cohort study.

Funder

Graduiertenkolleg

Publisher

Hindawi Limited

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism

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