Association of genetic variants with chronic kidney disease in individuals with different lipid profiles.
The purpose of the present study was to identify genetic variants that confer susceptibility to chronic kidney disease (CKD) in individuals with low or high serum concentrations of triglycerides (TG), high-density lipoprotein (HDL)-cholesterol, or low-density lipoprotein (LDL)-cholesterol, thereby contributing to the personalized prevention of CKD in such individuals. The study population comprised 5944 Japanese individuals, including 1706 subjects with CKD [estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2] and 4238 controls (eGFR>or=60 ml/min/1.73 m2). The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, and a stepwise forward selection procedure revealed that seven different polymorphisms were significantly (P<0.005) associated with the prevalence of CKD in individuals with low or high serum concentrations of TG or HDL- or LDL-cholesterol: the Aright curved arrow G (Glu23Lys) polymorphism of KCNJ11 and the 125592Cright curved arrow A (Thr431Asn) polymorphism of ROCK2 in individuals with low serum TG; the 734Cright curved arrow T (Thr254Ile) polymorphism of ACAT2 and the Cright curved arrow G (Gln27Glu) polymorphism of ADRB2 in individuals with high serum TG; the -1607/1Gright curved arrow 2G polymorphism of MMP1 in individuals with low serum HDL-cholesterol; the Gright curved arrow A (Val158Met) polymorphism of COMT in individuals with low serum LDL-cholesterol; the 584Gright curved arrow A (Gln192Arg) polymorphism of PON1 in individuals with high serum LDL-cholesterol. No polymorphism was associated with CKD in individuals with high serum HDL-cholesterol. These results suggest that polymorphisms associated with CKD may differ among individuals with different lipid profiles. Stratification of subjects according to lipid profiles 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
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics; D016009:Chi-Square Distribution; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D016015:Logistic Models; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D054460:rho-Associated Kinases / Q000235:genetics; D000099161:Kcnj11 Channel
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D043303:Aryldialkylphosphatase; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D020781:Matrix Metalloproteinase 1; D024661:Potassium Channels, Inwardly Rectifying; D014280:Triglycerides; D054460:rho-Associated Kinases; D000099161:Kcnj11 Channel; C515852:ROCK2 protein, human; C468406:PON1 protein, human; C522360:MMP1 protein, human