Association Between CNDP1 Genotype and Diabetic Nephropathy Is Sex Specific

• Published in: Diabetes (New York, N.Y.) Vol. 59; no. 6; pp. 1555 - 1559
• Main Authors: MOOYAART, Antien L, ZUTINIC, Ana, NAVIS, Gerjan, JANSSEN, Bart, BAELDE, Hans J, DE HEER, Emile, BAKKER, Stephan J. L, GROOTENDORST, Diana C, KLEEFSTRA, Nanne, VAN VALKENGOED, Irene G. M, BÖHRINGER, Stefan, BILO, Henk J. G, DEKKER, Friedo W, ANTHONIE BRUIJN, Jan
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2010
• Subjects: Age of Onset; Aged; Associated diseases and complications; Biological and medical sciences; Brief Report; Diabetes; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Diabetic nephropathies; Diabetic Nephropathies - genetics; Diabetic Nephropathies - prevention & control; Diabetic nephropathy; Dipeptidases - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; European Continental Ancestry Group - genetics; Female; Gene Frequency; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetic susceptibility; Genotype; Genotype & phenotype; Hemodialysis; Homozygote; Humans; Kidney diseases; Kidneys; Leucine; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Patients; Physiological aspects; Proteases; Reference Values; Repetitive Sequences, Amino Acid - genetics; Research design; Risk factors; Sex Characteristics; Type 2 diabetes; Urinary system involvement in other diseases. Miscellaneous; White people; Netherlands; Endocrinopathy; Kidney disease; Concomitant disease; Urinary system disease; Diabetes mellitus; Genotype; Diabetic nephropathy
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db09-1377

The 5-5 homozygous CNDP1 (carnosinase) genotype is associated with a reduced risk of diabetic nephropathy. We investigated whether this association is sex specific and independent of susceptibility for type 2 diabetes. Three separate groups of 114, 90, and 66 patients with type 2 diabetes and diabetic nephropathy were included in this study and compared with 93 patients with type 2 diabetes for >15 years without diabetic nephropathy and 472 population control subjects. The diabetes control group was used to determine an association in the three patient groups separately, and the population control group was used to estimate the genotype risk [odds ratio (CI)] for the population in a pooled analysis. The population control subjects were also compared with 562 patients with type 2 diabetes without diabetic nephropathy to determine whether the association was independent of type 2 diabetes. The CNDP1 genotype was determined by fragment analysis after PCR amplification. The frequency of the 5-5 homozygous genotype was 28, 36, and 41% in the three diabetic nephropathy patient groups and 43 and 42% in the diabetic and population control subjects, respectively. The 5-5 homozygous genotype occurred significantly less frequently in women in all three patient groups compared with diabetic control subjects. The genotype risk for the population was estimated to be 0.5 (0.30-0.68) in women and 1.2 (0.77-1.69) in men. The 562 patients with type 2 diabetes without diabetic nephropathy did not differ from the general population (P = 0.23). This study suggests that the association between the CNDP1 gene and diabetic nephropathy is sex specific and independent of susceptibility for type 2 diabetes.