title: Association of genetic variants with chronic kidney disease in Japanese individuals with type 2 diabetes mellitus.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yoshida
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yokoi
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Norifumi
authors.initials: N
authors.lastname: Metoki
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Kei
authors.initials: K
authors.lastname: Satoh
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishigaki
authors.forename: Takao
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nozawa
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
mesh_terms: 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
chemical_list: 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