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Identification of chromosome 3q28 and ALPK1 as susceptibility loci for chronic kidney disease in Japanese individuals by a genome-wide association study
  1. Yoshiji Yamada1,
  2. Tamotsu Nishida1,
  3. Sahoko Ichihara1,
  4. Kimihiko Kato1,2,
  5. Tetsuo Fujimaki3,
  6. Mitsutoshi Oguri4,
  7. Hideki Horibe5,
  8. Tetsuro Yoshida6,
  9. Sachiro Watanabe7,
  10. Kei Satoh8,
  11. Yukitoshi Aoyagi9,
  12. Michio Fukuda10,
  13. Motoji Sawabe11
  1. 1Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie, Japan
  2. 2Meitoh Hospital, Nagoya, Aichi, Japan
  3. 3Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie, Japan
  4. 4Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan
  5. 5Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu, Japan
  6. 6Department of Cardiovascular Medicine, Onga Nakama Medical Association Onga Hospital, Onga, Fukuoka, Japan
  7. 7Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gifu, Japan
  8. 8Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
  9. 9Department of Genomics for Longevity, Tokyo Metropolitan Institute of Gerontology, Tokyo, Tokyo, Japan
  10. 10Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
  11. 11Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Tokyo, Japan
  1. Correspondence to Professor Yoshiji Yamada, Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu, Mie 514-8507, Japan; yamada{at}gene.mie-u.ac.jp

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.

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