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• Genetic studies on metabolic disorder-associated kidney diseases.

  Imamura M, Kadowaki T, Maeda S

  Kidney international ( Kidney International )  108 ( 1 ) 30 - 37   2025.07 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• A variant in <i>HMMR/HMMR-AS1</i> is associated with serum alanine aminotransferase levels in the Ryukyu population

  Ohyama, N; Matsunami, M; Imamura, M; Yoshida, A; Javed, A; Liu, XX; Kimura, R; Matsuda, K; BioBank Japan Project; Terao, C; Maeda, S

  SCIENTIFIC REPORTS ( Scientific Reports )  15 ( 1 ) 6494 - 6494   2025.02 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  The Ryukyu archipelago is located southwest of the Japanese islands, and people originally from this region, the Ryukyu population, have a unique genetic background distinct from that of other populations, including people from mainland Japan. However, few genetic studies have focused on the Ryukyu population. In this study, we performed genome-wide association studies (GWAS) on the serum levels of alanine aminotransferase (ALT, n = 15,224), aspartate aminotransferase (AST, n = 15,203), and gamma-glutamyl transferase (GGT, n = 14,496) in the Ryukyu population. We found 13 loci with a genome-wide significant association (P < 5 × 10-8), three for ALT, four for AST, and six for GGT, including one novel locus associated with ALT: rs117595134-A in HMMR/HMMR-AS1, ß =  - 0.131, standard error = 0.024, P = 4.90 × 10-8. Rs117595134-A is common in the Japanese population but is not observed in other ethnic populations in the 1000 genomes database. Additionally, 77 of 80 loci derived from Korean GWAS and 541 of 716 loci from European GWAS showed the same directions of effect (P = 1.41 × 10-19, P = 2.50 × 10-44, binomial test), indicating that most of susceptibility loci are shared between the Ryukyu population and other ethnic populations.

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• Genetic studies of type 2 diabetes, and microvascular complications of diabetes

  Imamura, M; Maeda, S

  DIABETOLOGY INTERNATIONAL ( Diabetology International )  15 ( 4 ) 699 - 706   2024.10 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Genome-wide association studies for pelvic organ prolapse in the Japanese population

  Matsunami, M; Imamura, M; Ashikari, A; Liu, XX; Tomizuka, K; Hikino, K; Miwa, K; Kadekawa, K; Suda, T; Matsuda, K; Miyazato, M; Terao, C; Maeda, S

  COMMUNICATIONS BIOLOGY ( Nature Research )  7 ( 1 ) 1188 - 9   2024.09 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Pelvic organ prolapse (POP) affects approximately 40% of elderly women, characterized by thedescent of the pelvic organs into the vaginal cavity. Here we present the results of a genome-wideassociation study (GWAS) for susceptibility to POP comprising 771 cases and 76,625 controls in theJapanese population. We identified a significant association of WT1 locus with POP in the Japanesepopulation; rs10742277; odds ratio (OR) = 1.48, 95% confidence interval (CI), 1.29–1.68,P = 6.72 × 10−9. Subsequent cross-ancestry GWAS meta-analysis combining the Japanese data andpreviously reported European data, including 28,857 cases and 622,916 controls, identified FGFR2locus as a novel susceptibility locus to POP (rs7072877; OR = 1.06, 95% CI, 1.04–1.08,P = 4.11 × 10−8). We also observed consistent directions of the effects for 21 out of 24 European GWASderived loci (binomial test P = 2.8 × 10−4), indicating that most of susceptibility loci for POP are sharedacross the Japanese and European populations.

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• Perspectives on genetic studies of type 2 diabetes from the genome-wide association studies era to precision medicine

  Imamura M, Maeda S

  Journal of Diabetes Investigation ( John Wiley & Sons Australia, Ltd )  15 ( 4 ) 410 - 422   2024.01 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Genome-wide association study for type 2 diabetes

  Imamura M. ( Part: Allotment Writing )

  Genome-Wide Association Studies  2019.01

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• Human genetics of Type 2 Diabetes and Its Clinical Implications

  Imamura Minako

  Journal of the Japan Diabetes Society ( THE JAPAN DIABETES SOCIETY )  65 ( 4 ) 179 - 182   2022.04

   

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• Susceptible Genes for Diabetic Retinopathy

  Imamura Minako, Maeda Shiro

  Journal of the Japan Diabetes Society ( THE JAPAN DIABETES SOCIETY )  62 ( 11 ) 702 - 706   2019

   

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• Grant-in-Aid for Scientific Research(C)

  Project Year: 2020.04  -  2023.03 

  Direct: 3,300,000 (YEN)  Overheads: 4,290,000 (YEN)  Total: 990,000 (YEN)

• Identification of novel therapeutic target for type 2 diabetes through genome-based drug discovery

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2017.04  -  2020.03 

  Investigator(s): Imamura Minako 

  Direct: 3,500,000 (YEN)  Overheads: 4,550,000 (YEN)  Total: 1,050,000 (YEN)

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  Genome-wide association studies (GWAS) have identified more than 200 genetic loci associated with susceptibility for type 2 diabetes (T2D). We have previously proposed several new potential pharmacological targets for T2D treatments using systematic bioinformatics approach integrating the findings of GWAS for T2D, and biological or pharmacological information from various databases. KIF11 is one of the potential therapeutic targets identified by the in silico pipeline. We have demonstrated that administration of KIF11 inhibitor ameliorated impaired glucose tolerance on db/db mice through increasing the insulin sensitivity and suppressing hepatic glucose production. The results suggest that our GWAS-based drug discovery platform is useful to identify novel drug targets for the treatment of common diseases, such as T2D.

• Functional analysis of GWAS-derived type 2 diabetes susceptibility genes

  Grant-in-Aid for Scientific Research(C)

  Project Year: 2014.04  -  2017.03 

  Investigator(s): IMAMURA Minako 

  Direct: 3,800,000 (YEN)  Overheads: 4,940,000 (YEN)  Total: 1,140,000 (YEN)

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  We have performed a fine-mapping within the C2CD4A-C2CD4B locus to identify causal variants for type 2 diabetes susceptibility. The most significant association was observed in intergenic region which indicates the causal variant may affect the expression of either C2CD4A or C2CD4B. We also found that these genes dominantly expressed in human pancreas and mouse pancreatic beta cell line. Motivated by the results of fine mapping and expression analysis, we have generated beta-cell specific transgenic mice for C2cd4a and C2cd4b respectively to evaluate the role of these genes in vivo.

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• 2023.09