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

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

doi:10.1007/s00125-010-1863-0

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

27 Citations (Scopus)

Abstract

Aims/hypothesis Homozygosity 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 I 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).

Methods In 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

Results The 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/interpretation CNDP1 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.

Original language	English
Pages (from-to)	2562 - 2568
Number of pages	7
Journal	Diabetologia
Volume	53
Issue number	12
DOIs	https://doi.org/10.1007/s00125-010-1863-0
Publication status	Published - Dec-2010

Keywords

Carnosinase gene
CNDP1
Diabetic nephropathy
End-stage renal disease
Five leucine repeat
Type 1 diabetes
AFRICAN-AMERICANS
LEUCINE REPEAT
SUSCEPTIBILITY
ASSOCIATION
CELLS
COMPLICATIONS
SECRETION
SYSTEM
TRENDS
RISK

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Alkhalaf, A., Bakker, S. J. L., Bilo, H. J. G., Gans, R. O. B., Navis, G. J., Postmus, D., Forsblom, C., Groop, P. H., Vionnet, N., Hadjadj, S., Marre, M., Parving, H. H., Rossing, P., & Tarnow, L. (2010). 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. Diabetologia, 53(12), 2562 - 2568. https://doi.org/10.1007/s00125-010-1863-0

@article{ab0fd557eb854bf9981ab7ef5e62ff16,

title = "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",

abstract = "Aims/hypothesis Homozygosity 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 I 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).Methods In 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) normoalbuminuriaResults The 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/interpretation CNDP1 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.",

keywords = "Carnosinase gene, CNDP1, Diabetic nephropathy, End-stage renal disease, Five leucine repeat, Type 1 diabetes, AFRICAN-AMERICANS, LEUCINE REPEAT, SUSCEPTIBILITY, ASSOCIATION, CELLS, COMPLICATIONS, SECRETION, SYSTEM, TRENDS, RISK",

author = "A. Alkhalaf and Bakker, \{S. J. L.\} and Bilo, \{H. J. G.\} and Gans, \{R. O. B.\} and Navis, \{G. J.\} and D. Postmus and C. Forsblom and Groop, \{P. H.\} and N. Vionnet and S. Hadjadj and M. Marre and Parving, \{H. H.\} and P. Rossing and L. Tarnow",

note = "Article",

year = "2010",

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doi = "10.1007/s00125-010-1863-0",

language = "English",

volume = "53",

pages = "2562 -- 2568",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "12",

}

Alkhalaf, A, Bakker, SJL , Bilo, HJG , Gans, ROB , Navis, GJ , Postmus, D, Forsblom, C, Groop, PH, Vionnet, N, Hadjadj, S, Marre, M, Parving, HH, Rossing, P & Tarnow, L 2010, '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', Diabetologia, vol. 53, no. 12, pp. 2562 - 2568. https://doi.org/10.1007/s00125-010-1863-0

TY - JOUR

T1 - 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

AU - Alkhalaf, A.

AU - Bakker, S. J. L.

AU - Bilo, H. J. G.

AU - Gans, R. O. B.

AU - Navis, G. J.

AU - Postmus, D.

AU - Forsblom, C.

AU - Groop, P. H.

AU - Vionnet, N.

AU - Hadjadj, S.

AU - Marre, M.

AU - Parving, H. H.

AU - Rossing, P.

AU - Tarnow, L.

N1 - Article

PY - 2010/12

Y1 - 2010/12

N2 - Aims/hypothesis Homozygosity 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 I 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).Methods In 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) normoalbuminuriaResults The 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/interpretation CNDP1 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.

AB - Aims/hypothesis Homozygosity 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 I 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).Methods In 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) normoalbuminuriaResults The 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/interpretation CNDP1 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.

KW - Carnosinase gene

KW - CNDP1

KW - Diabetic nephropathy

KW - End-stage renal disease

KW - Five leucine repeat

KW - Type 1 diabetes

KW - AFRICAN-AMERICANS

KW - LEUCINE REPEAT

KW - SUSCEPTIBILITY

KW - ASSOCIATION

KW - CELLS

KW - COMPLICATIONS

KW - SECRETION

KW - SYSTEM

KW - TRENDS

KW - RISK

U2 - 10.1007/s00125-010-1863-0

DO - 10.1007/s00125-010-1863-0

M3 - Article

C2 - 20711718

SN - 0012-186X

VL - 53

SP - 2562

EP - 2568

JO - Diabetologia

JF - Diabetologia

IS - 12

ER -

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

Abstract

Keywords

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