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

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.

• Authors: A Alkhalaf, G W D Landman, K J J van Hateren, K H Groenier, A L Mooyaart, E De Heer, R O B Gans, G J Navis, S J L Bakker, N Kleefstra, H J G Bilo
• Journal: Journal of nephrology (J Nephrol) Vol. 28 Issue 2 Pg. 201-7 (Apr 2015) ISSN: 1724-6059 [Electronic] Italy
• PMID: 24756973 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CNDP1 protein, human
• Dipeptidases
• Leucine

Topics

• Aged
• Cardiovascular Diseases (genetics, mortality)
• Diabetes Mellitus, Type 2 (genetics)
• Diabetic Nephropathies (genetics, physiopathology)
• Dipeptidases (genetics)
• Disease Progression
• Female
• Follow-Up Studies
• Glomerular Filtration Rate (genetics)
• Homozygote
• Humans
• Leucine (genetics)
• Male
• Middle Aged
• Polymorphism, Genetic
• Proportional Hazards Models
• Prospective Studies
• Sex Factors