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.
Yoshida
Tetsuro
T
Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan.
Kato
Kimihiko
K
Yokoi
Kiyoshi
K
Oguri
Mitsutoshi
M
Watanabe
Sachiro
S
Metoki
Norifumi
N
Yoshida
Hidemi
H
Satoh
Kei
K
Aoyagi
Yukitoshi
Y
Nishigaki
Yutaka
Y
Nozawa
Yoshinori
Y
Yamada
Yoshiji
Y
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