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Sex specific association between carnosinase gene CNDP1 and cardiovascular mortality in patients with type 2 diabetes (ZODIAC-22)

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Abstract

Introduction

Homozygosity for a 5-leucine repeat (5L-5L) in the carnosinase gene (CNDP1) has been associated with a reduced prevalence of diabetic nephropathy in cross-sectional studies in patients with type 2 diabetes, particularly in women. Prospective studies on mortality are not available. This study investigated whether 5L-5L was associated with mortality and progression of renal function loss and to what extent this effect is modified by sex.

Methods

In a prospective cohort of patients with type 2 diabetes, a Cox proportional hazard model was used to compare 5L-5L with other genotypes regarding (cardiovascular) mortality. Renal function slopes were obtained by within-individual linear regression of the estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation, and were compared between 5L-5L and other genotypes.

Results

871 patients were included (38 % with 5L-5L). After 9.5 years of follow-up, hazards ratios (HR) for all-cause and cardiovascular mortality in 5L-5L versus other genotypes were 1.09 [95 % confidence interval (CI) 0.88–1.36] and 1.12 (95 % CI 0.79–1.58), respectively. There was a significant interaction between CNDP1 and sex for the association with cardiovascular mortality (p = 0.01), not for all-cause mortality (p = 0.32). Adjusted HR in 5L-5L for cardiovascular mortality was 0.69 (95 % CI 0.39–1.23) in men and 1.77 (95 % CI 1.12–2.81) in women. The slopes of eGFR-MDRD did not significantly differ between 5L-5L and other genotypes.

Conclusions

The association between CNDP1 and cardiovascular mortality was sex-specific, with a higher risk in women with 5L-5L genotype. CNDP1 was not associated with all-cause mortality or change in eGFR.

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Abbreviations

CNDP1 :

Carnosinase gene 1

5L-5L:

Homozygosity for 5-leucin repeat

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Acknowledgments

This study was funded by the medical research foundation in Zwolle, the Netherlands, and a grant from the European Union to PREDICTIONS (Prevention of Diabetes Complication) network.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Diabetes Centre, Isala Clinics, Dr. Spanjaardweg 11, P.O. Box 10400, 8000 GK, Zwolle, The Netherlands

    A. Alkhalaf, G. W. D. Landman, K. J. J. van Hateren, K. H. Groenier, N. Kleefstra & H. J. G. Bilo

  2. Department of Gastroenterology, Isala Clinics, Zwolle, The Netherlands

    A. Alkhalaf

  3. Department of General Practice, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    K. H. Groenier

  4. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

    A. L. Mooyaart & E. De Heer

  5. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    R. O. B. Gans, G. J. Navis, S. J. L. Bakker, N. Kleefstra & H. J. G. Bilo

  6. Langerhans Medical Research Group, Zwolle, The Netherlands

    N. Kleefstra

  7. Department of Internal Medicine, Isala Clinics, Zwolle, The Netherlands

    H. J. G. Bilo

  8. Department of Internal Medicine, Gelre Hospital, Apeldoorn, The Netherlands

    G. W. D. Landman

Authors
  1. A. Alkhalaf
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  2. G. W. D. Landman
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  3. K. J. J. van Hateren
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  4. K. H. Groenier
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  5. A. L. Mooyaart
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  6. E. De Heer
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  7. R. O. B. Gans
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  8. G. J. Navis
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  9. S. J. L. Bakker
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  10. N. Kleefstra
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  11. H. J. G. Bilo
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Corresponding author

Correspondence to G. W. D. Landman.

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Alkhalaf, A., Landman, G.W.D., van Hateren, K.J.J. et al. Sex specific association between carnosinase gene CNDP1 and cardiovascular mortality in patients with type 2 diabetes (ZODIAC-22). J Nephrol 28, 201–207 (2015). https://doi.org/10.1007/s40620-014-0096-6

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  • DOI: https://doi.org/10.1007/s40620-014-0096-6

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