Abstract

Objectives: Recently, an association was found between diabetic nephropathy and the D18S880 microsatellite, located in the carnosinase gene (CNDP1) on chro-mosome 18q. Alleles of this microsatellite encode for a variable number of leucine residues (from 4 to 7) in the leader peptide of the carnosinase precursor. The homozygous for the 5 leucines were more common in controls than cases in studies focusing on type 2 diabetic patients. To test whether this finding can be extended to type 1 diabetic patients, we carried out a comprehensive study on association between diabetic nephropathy and the D18S880 microsatellite and 21 additional SNPs that tagged the genomic region containing CNDP1 and CNDP2.

Methods: Overall, 1269 Caucasian patients with type 1 diabetes were included in the study: 613 patients with normoalbuminuria and long duration of diabetes, 445 patients with persistent proteinuria, and 211 patients with end stage renal disease. All patients were genotyped for selected polymorphisms and the associations with diabetic nephropathy were tested by χ2 test with calculating odds ratios.

Results: We did not find any significant association between diabetic nephropathy and any examined genetic markers. The negative findings of the case – control study were supported further by negative findings obtained from the six-year follow-up study of 445 patients with persistent proteinuria during which 135 patients developed ESRD.

Conclusion: Our large comprehensive study did not find the association of the D18S880 microsatellite nor any other polymorphisms in the CNDP2 – CNDP1 genomic region and susceptibility for diabetic nephropathy in type 1 diabetes.