In view of a polymorphism in the carnosinase 1 gene CNDP1, resulting in reduced carnosine degradation activity and a significant DN risk reduction, carnosine (β-alanyl-L-histidine) has gained attention as a potential therapeutic target.
Low serum carnosinase (CN-1) concentrations are associated with low risk for development of diabetic nephropathy (DN) in patients with type 2 diabetes (T2D).
CNDP1 (CTG)<sub>5</sub> homozygous patients with T2D with DN had significantly lower CNDP1 concentrations (30.4 ± 18.3 vs 51.2 ± 17.6 µg/ml, p < 0.05) and activity (1.25 ± 0.5 vs 2.53 ± 1.1 µmol/ml/h, p < 0.05) than those without nephropathy.
To evaluate the impact of the CNDP1 Mannheim allele on pediatric chronic kidney disease (CKD), we prospectively followed the long-term clinical outcome of 272 children with non-diabetic kidney disease (glomerulopathies n=32, non-glomerular kidney disease n=240).
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.
Carnosinase 1 (CN1) contributes to diabetic nephropathy by cleaving histidine-dipeptides which scavenge reactive oxygen and carbonyl species and increase nitric oxide (NO) production.
The authors conducted meta-analysis on association between the CNDP1 D18S880 microsatellite polymorphism and DN susceptibility, using fixed and random effects models.
In this study, we examined the association of polymorphisms within the CNDP1/CNDP 2 locus with diabetic nephropathy in Japanese subjects with type 2 diabetes.
Recently, we identified an allelic variant of human carnosinase 1 (CN1) that results in increased enzyme activity and is associated with susceptibility for diabetic nephropathy in humans.
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).
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).
CNDP1 polymorphism was not associated with mortality, and nor was there an interaction of this polymorphism with DN for prediction of mortality in patients with type 1 diabetes.
This study suggests that the association between the CNDP1 gene and diabetic nephropathy is sex specific and independent of susceptibility for type 2 diabetes.
We investigated the frequency of the 5/5 homozygous CNDP1 (carnosinase) genotype, which was found to be associated with a reduced risk of developing diabetic nephropathy, in three ethnic groups in The Netherlands.
Protection from diabetic nephropathy afforded by 5L-5L homozygosity in CNDP1 may be masked by the effects of additional risk haplotypes in CNDP1 and CNDP2.
Our large, comprehensive study did not find an association between the D18S880 microsatellite or any other polymorphisms in the CNDP2-CNDP1 genomic region and susceptibility for diabetic nephropathy in type 1 diabetes.
Our large, comprehensive study did not find an association between the D18S880 microsatellite or any other polymorphisms in the CNDP2-CNDP1 genomic region and susceptibility for diabetic nephropathy in type 1 diabetes.