Association of genetic variants with chronic kidney disease in Japanese individuals with type 2 diabetes mellitus.
Although diabetes mellitus has been recognized as a risk factor for chronic kidney disease (CKD), genetic factors for predisposition to CKD in individuals with diabetes mellitus remain elucidated. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD among individuals with type 2 diabetes mellitus. The study population comprised 1742 Japanese individuals, including 636 subjects with CKD [estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2] and 1106 controls (eGFR>or=60 ml/min/1.73 m2). The genotypes for 24 polymorphisms of 22 candidate genes were determined. An initial screen of allele frequencies by the Chi-square test revealed that four polymorphisms were significantly (false discovery rate<0.05) associated with the prevalence of CKD in individuals with type 2 diabetes mellitus. Subsequent multivariable logistic regression analysis with adjustment for covariates as well as a stepwise forward selection procedure revealed that the 8733T-->C polymorphism of ALOX5AP (rs3803278), the C-->T (Ser532Leu) polymorphism of IRAK1 (rs1059703), and the 2445G-->A (Ala54Thr) polymorphism of FABP2 (rs1799883) were significantly (P<0.05) associated with the prevalence of CKD. Our results suggest that ALOX5AP, IRAK1, and FABP2 are susceptibility loci for CKD among Japanese individuals with type 2 diabetes mellitus.
Yoshida
Tetsuro
T
Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan.
Kato
Kimihiko
K
Yokoi
Kiyoshi
K
Watanabe
Sachiro
S
Metoki
Norifumi
N
Yoshida
Hidemi
H
Satoh
Kei
K
Aoyagi
Yukitoshi
Y
Nishigaki
Yutaka
Y
Suzuki
Takao
T
Nozawa
Yoshinori
Y
Yamada
Yoshiji
Y
D058927:5-Lipoxygenase-Activating Proteins; D000368:Aged; D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics; D007564:Japan; D007676:Kidney Failure, Chronic / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; D008565:Membrane Proteins; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases