Association of gene polymorphisms with chronic kidney disease in high- or low-risk subjects defined by conventional risk factors.
The purpose of the present study was to identify genetic variants which confer susceptibility to chronic kidney disease (CKD) in high- or low-risk subjects defined by conventional risk factors separately. The study population comprised 2828 Japanese individuals, including 434 subjects with CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)] and 2394 controls (eGFR > or =60 ml/min/ 1.73 m(2)). The 1012 high-risk subjects had both hypertension and diabetes mellitus, and the 1816 low-risk subjects had none of these conditions. The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that ten different polymorphisms were associated (P<0.05) with the prevalence of CKD in high- or low-risk subjects: the -519Aright curved arrow G polymorphism of MMP1, the 1061Aright curved arrow G (Ile405Val) polymorphism of CETP, the Aright curved arrow G (Lys45Glu) polymorphism of MMP3, the -219Gright curved arrow T polymorphism of APOE, the Aright curved arrow G (Ile1205Val) polymorphism of COL3A1, the -863Cright curved arrow A polymorphism of TNF, and the 1454Cright curved arrow G (Leu125Val) polymorphism of PECAM1 in high-risk subjects; and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2, the 2386Aright curved arrow G (Ile796Val) polymorphism of SCAP, and the TAAAright curved arrow del polymorphism of PDE4D in low-risk subjects. Among these polymorphisms, the -519Aright curved arrow G polymorphism of MMP1 and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2 were most significantly associated with CKD in high- or low-risk individuals, respectively. These results suggest that polymorphisms associated with CKD may differ among high- or low-risk subjects. Stratification of subjects according to conventional risk factors may thus be important for personalized prevention of CKD based on genetic information.
Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan.
Tetsuro
T
Yoshida
Kimihiko
K
Kato
Kiyoshi
K
Yokoi
Mitsutoshi
M
Oguri
Sachiro
S
Watanabe
Norifumi
N
Metoki
Hidemi
H
Yoshida
Kei
K
Satoh
Yukitoshi
Y
Aoyagi
Yutaka
Y
Nishigaki
Yoshinori
Y
Nozawa
Yoshiji
Y
Yamada
D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000235:genetics; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007674:Kidney Diseases / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D012307:Risk Factors
D001057:Apolipoproteins E; C506642:CETP protein, human; C439971:COL3A1 protein, human; D053480:Cholesterol Ester Transfer Proteins; D024061:Collagen Type III; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018125:Receptors, Transforming Growth Factor beta; C102196:SREBP cleavage-activating protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1