Exclusion of Polymorphisms in Carnosinase Genes (CNDP1 and CNDP2) as a Cause of Diabetic Nephropathy in Type 1 Diabetes : Results of Large Case-Control and Follow-Up Studies

Recently, an association was found between diabetic nephropathy and the D18S880 microsatellite, located in the carnosinase gene (CNDP1) on chromosome 18q. Alleles of this microsatellite encode for a variable number of leucine residues (from four to seven) in the leader peptide of the carnosinase pre...

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Vydáno v:Diabetes (New York, N.Y.) Ročník 57; číslo 9; s. 2547 - 2551
Hlavní autoři: WANIC, Krzysztof, PLACHA, Grzegorz, DUNN, Jonathon, SMILES, Adam, WARRAM, James H, KROLEWSKI, Andrzej S
Médium: Journal Article
Jazyk:angličtina
Vydáno: Alexandria, VA American Diabetes Association 01.09.2008
Témata:
Adult
Associated diseases and complications
Biological and medical sciences
Case-Control Studies
Control
Creatinine
Diabetes
Diabetes Mellitus, Type 1 - epidemiology
Diabetes Mellitus, Type 1 - genetics
Diabetes. Impaired glucose tolerance
Diabetic nephropathies
Diabetic Nephropathies - epidemiology
Diabetic Nephropathies - genetics
Diabetic nephropathy
Diabetics
Dipeptidases - genetics
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
Follow-Up Studies
Genes
Genetic aspects
Genetic polymorphisms
Genetic Predisposition to Disease - epidemiology
Genetics
Genotype
Health aspects
Humans
Incidence
Kidney diseases
Kidneys
Male
Medical examination
Medical sciences
Microsatellite Repeats
Middle Aged
Nephrology. Urinary tract diseases
Peptides
Physiological aspects
Polymorphism, Single Nucleotide
Research design
Risk Factors
Urinary system involvement in other diseases. Miscellaneous
White people
Poland
Endocrinopathy
Kidney disease
Immunopathology
Concomitant disease
Urinary system disease
Gene
Type 1 diabetes
Follow up study
Autoimmune disease
Diabetic nephropathy
Polymorphism
ISSN:0012-1797, 1939-327X, 1939-327X
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Shrnutí:Recently, an association was found between diabetic nephropathy and the D18S880 microsatellite, located in the carnosinase gene (CNDP1) on chromosome 18q. Alleles of this microsatellite encode for a variable number of leucine residues (from four to seven) in the leader peptide of the carnosinase precursor. The frequency of subjects homozygous for the five leucines was higher in control subjects than in case subjects 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. Overall, 1,269 Caucasian patients with type 1 diabetes were included in the study, including 613 patients with normoalbuminuria and a long duration of diabetes, 445 patients with persistent proteinuria, and 211 patients with end-stage renal disease (ESRD). All patients were genotyped for selected polymorphisms, the associations with diabetic nephropathy were tested by a chi(2) test, and odds ratios were calculated. 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 6-year follow-up study of 445 patients with persistent proteinuria, during which 135 patients developed ESRD. 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.
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SourceType-Scholarly Journals-1
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Corresponding author: Andrzej S. Krolewski, andrzej.krolewski@joslin.harvard.edu
Published ahead of print at http://diabetes.diabetesjournals.org on 15 June 2008.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
ISSN:0012-1797
1939-327X
1939-327X
DOI:10.2337/db07-1303