The influence of a single nucleotide polymorphism within CNDP1 on susceptibility to diabetic nephropathy in Japanese women with type 2 diabetes

Several linkage analyses have mapped a susceptibility locus for diabetic nephropathy to chromosome 18q22-23, and polymorphisms within the carnosine dipeptidase 1 gene (CNDP1), located on 18q22.3, have been shown to be associated with diabetic nephropathy in European subjects with type 2 diabetes. Ho...

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Published in:PloS one 2013-01, Vol.8 (1), p.e54064-e54064
Main Authors: Kurashige, Mahiro, Imamura, Minako, Araki, Shin-Ichi, Suzuki, Daisuke, Babazono, Tetsuya, Uzu, Takashi, Umezono, Tomoya, Toyoda, Masao, Kawai, Koichi, Imanishi, Masahito, Hanaoka, Kazushige, Maegawa, Hiroshi, Uchigata, Yasuko, Hosoya, Tatsuo, Maeda, Shiro
Format: Article
Language:English
Subjects:
African Americans
Aged
Analysis
Asian Continental Ancestry Group - genetics
Biology
Carnosine
Chromosome 18
Chronic kidney failure
Confidence intervals
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - genetics
Diabetic nephropathies
Diabetic Nephropathies - genetics
Diabetic nephropathy
Diabetic retinopathy
Dipeptidase
Dipeptidases - genetics
Disease control
Disease susceptibility
End-stage renal disease
Endocrinology
Female
Genes
Genetic aspects
Genetic Predisposition to Disease
Genomes
Hospitals
Humans
Hypertension
Internal medicine
Kidney diseases
Kidney transplantation
Laboratories
Leucine
Loci
Male
Medicine
Metabolism
Middle Aged
Musculoskeletal system
Nephrology
Nephropathy
Polymorphism
Polymorphism, Single Nucleotide - genetics
Population studies
Proteinuria
Proteinuria - genetics
Regression analysis
Rodents
Science
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Statistical analysis
Studies
Susceptibility
Type 2 diabetes
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Summary:Several linkage analyses have mapped a susceptibility locus for diabetic nephropathy to chromosome 18q22-23, and polymorphisms within the carnosine dipeptidase 1 gene (CNDP1), located on 18q22.3, have been shown to be associated with diabetic nephropathy in European subjects with type 2 diabetes. However, the association of this locus with diabetic nephropathy has not been evaluated in the Japanese population. 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. We genotyped a leucine repeat polymorphism (D18S880) that is within CNDP1 along with 29 single nucleotide polymorphisms (SNPs) in the CNDP1/CNDP2 locus for 2,740 Japanese subjects with type 2 diabetes (1,205 nephropathy cases with overt nephropathy or with end-stage renal disease [ESRD], and 1,535 controls with normoalbuminuria). The association of each polymorphism with diabetic nephropathy was analysed by performing logistic regression analysis. We did not observe any association between D18S880 and diabetic nephropathy in Japanese subjects with type 2 diabetes. None of the 29 SNPs within the CNDP1/CNDP2 locus were associated with diabetic nephropathy, but a subsequent sex-stratified analysis revealed that 1 SNP in CNDP1 was nominally associated with diabetic nephropathy in women (rs12604675-A; p = 0.005, odds ratio [OR] = 1.76, 95% confidence interval [CI], 1.19-2.61). Rs12604675 was associated with overt proteinuria (p = 0.002, OR = 2.18, 95% CI, 1.32-3.60), but not with ESRD in Japanese women with type 2 diabetes. Rs12604675-A in CNDP1 may confer susceptibility to overt proteinuria in Japanese women with type 2 diabetes.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0054064