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Diabetologia. 2011 Sep;54(9):2295-302. doi: 10.1007/s00125-011-2178-5. Epub 2011 May 15.

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

Author information

1
Department of Clinical Sciences-Diabetes and Endocrinology, Lund University Diabetes Centre, Clinical Research Centre, University Hospital Skane, UMAS, 20502 Malmo, Sweden. Tarun.Ahluwalia@med.lu.se

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.

PMID:
21573905
DOI:
10.1007/s00125-011-2178-5
[Indexed for MEDLINE]
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