Association of genetic variants with chronic kidney disease in Japanese individuals.
OBJECTIVE
Although genetic linkage analyses and association studies have implicated several loci and candidate genes in predisposition to chronic kidney disease (CKD), the genes that underlie genetic susceptibility to this condition have remained uncharacterized. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in Japanese individuals.


METHODS
The study population comprised 5217 Japanese individuals (2955 men, 2262 women), including 778 subjects (480 men, 298 women) with CKD [estimated GFR (eGFR), <50 ml min(-1) 1.73 m(-2)] and 4439 controls (2475 men, 1964 women; eGFR, > or =60 ml min(-1) 1.73 m(-2)). The genotypes for 40 polymorphisms of 32 candidate genes were determined.


RESULTS
The chi-square test and multivariable logistic regression analysis with adjustment for covariates revealed that the -219G-->T polymorphism of APOE, the -519A-->G of MMP1, the -866G-->A of UCP2, the -1607/1G-->2G of MMP1, the A-->G (Lys45Glu) of MMP3, the G-->A (Ala163Thr) of AGTR1, the G-->A (Gly670Arg) of PECAM1, and the -55C-->T of UCP3 were significantly (false discovery rate <0.05) associated with CKD. Comparison of allele frequencies of these polymorphisms by the chi-square test between subgroups of CKD and control subjects individually matched for covariates revealed that the -519A-->G of MMP1 and the -866G-->A of UCP2 were significantly (P < 0.05) associated with CKD.


CONCLUSIONS
MMP1 and UCP2 may be susceptibility loci for CKD in Japanese individuals. Determination of genotypes for these polymorphisms may prove informative for prediction of genetic risk for CKD.
Yoshida
Tetsuro
T
Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan.
Kato
Kimihiko
K
Fujimaki
Tetsuo
T
Yokoi
Kiyoshi
K
Oguri
Mitsutoshi
M
Watanabe
Sachiro
S
Metoki
Norifumi
N
Yoshida
Hidemi
H
Satoh
Kei
K
Aoyagi
Yukitoshi
Y
Nishigaki
Yutaka
Y
Tanaka
Masashi
M
Nozawa
Yoshinori
Y
Kimura
Genjiro
G
Yamada
Yoshiji
Y
D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D015999:Multivariate Analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000208:ethnology* / Q000235:genetics*; D012307:Risk Factors; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D001057:Apolipoproteins E; D007473:Ion Channels; D024101:Mitochondrial Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D044140:Receptor, Angiotensin, Type 1; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1