title: Identification of chromosome 3q28 and ALPK1 as susceptibility loci for chronic kidney disease in Japanese individuals by a genome-wide association study.
abstract: BACKGROUND
  Although genome-wide association studies (GWASs) have implicated several genes in the predisposition to chronic kidney disease (CKD) in Caucasian or African American populations, the genes that confer susceptibility to CKD in Asian populations remain to be identified definitively. We performed a GWAS to identify genetic variants that confer susceptibility to CKD in Japanese individuals.
  
  
  METHODS
  3851 Japanese individuals from three independent subject panels were examined. Subject panels A, B, and C comprised 252, 910, and 190 individuals with CKD and 249, 838, and 1412 controls, respectively. A GWAS for CKD was performed in subject panel A.
  
  
  RESULTS
  Five single nucleotide polymorphisms (SNPs) at chromosome 3q28, ALPK1, FAM78B, and UMODL1 were significantly (false discovery rate<0.05) associated with CKD by the GWAS. The relation of these five SNPs and of an additional 22 SNPs at these loci to CKD was examined in subject panel B, revealing that rs9846911 at 3q28 was significantly associated with CKD in all individuals and that rs2074381 and rs2074380 in ALPK1 were associated with CKD in individuals with diabetes mellitus. These three SNPs were further examined in subject panel C, revealing that rs2074381 and rs2074380 were significantly associated with CKD. For subject panels B and C combined, rs9846911 was significantly associated with CKD in all individuals and rs2074381 and rs2074380 were associated with CKD in diabetic individuals.
  
  
  CONCLUSIONS
  Chromosome 3q28 may be a susceptibility locus for CKD in Japanese individuals, and ALPK1 may be a susceptibility gene for CKD in such individuals with diabetes mellitus.
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu, Mie 514-8507, Japan. yamada@gene.mie-u.ac.jp
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Nishida
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ichihara
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.forename: Hideki
authors.initials: H
authors.lastname: Horibe
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yoshida
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kei
authors.initials: K
authors.lastname: Satoh
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Michio
authors.initials: M
authors.lastname: Fukuda
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D048909:Diabetes Complications / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011494:Protein Kinases / Q000235:genetics*; D051436:Renal Insufficiency, Chronic / Q000235:genetics*
chemical_list: D011494:Protein Kinases