Common variants in CNDP1 and CNDP2, and risk of nephropathy in type 2 diabetes.

Abstract

AIMS/HYPOTHESIS:

Several genome-wide linkage studies have shown an association between diabetic nephropathy and a locus on chromosome 18q harbouring two carnosinase genes, CNDP1 and CNDP2. Carnosinase degrades carnosine (β-alanyl-L-histidine), which has been ascribed a renal protective effect as a scavenger of reactive oxygen species. We investigated the putative associations of genetic variants in CNDP1 and CNDP2 with diabetic nephropathy (defined either as micro- or macroalbuminuria) and estimated GFR in type 2 diabetic patients from Sweden.

METHODS:

We genotyped nine single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (D18S880, five to seven leucine repeats) in CNDP1 and CNDP2 in a case-control set-up including 4,888 unrelated type 2 diabetic patients (with and without nephropathy) from Sweden (Scania Diabetes Registry).

RESULTS:

Two SNPs, rs2346061 in CNDP1 and rs7577 in CNDP2, were associated with an increased risk of diabetic nephropathy (rs2346061 p = 5.07 × 10(-4); rs7577 p = 0.021). The latter was also associated with estimated GFR (β = -0.037, p = 0.014), particularly in women. A haplotype including these SNPs (C-C-G) was associated with a threefold increased risk of diabetic nephropathy (OR 2.98, 95% CI 2.43-3.67, p < 0.0001).

CONCLUSIONS/INTERPRETATION:

These data suggest that common variants in CNDP1 and CNDP2 play a role in susceptibility to kidney disease in patients with type 2 diabetes.

• Authors: T S Ahluwalia, E Lindholm, L C Groop
• Journal: Diabetologia (Diabetologia) Vol. 54 Issue 9 Pg. 2295-302 (Sep 2011) ISSN: 1432-0428 [Electronic] Germany
• PMID: 21573905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CNDP1 protein, human
• Dipeptidases
• CNDP2 protein, human

Topics

• Adult
• Aged
• Albuminuria (physiopathology)
• Case-Control Studies
• Diabetes Mellitus, Type 2 (complications, ethnology, genetics)
• Diabetic Nephropathies (epidemiology, genetics, physiopathology)
• Dipeptidases (genetics)
• Female
• Genetic Predisposition to Disease (genetics)
• Genotype
• Glomerular Filtration Rate (physiology)
• Haplotypes (genetics)
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Risk Factors
• Sweden
• Trinucleotide Repeats (genetics)