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Replication study for the association of 3 SNP loci identified in a genome-wide association study for diabetic nephropathy in European type 1 diabetes with diabetic nephropathy in Japanese patients with type 2 diabetes

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Abstract

Background

A recent genome-wide association study for diabetic nephropathy in European type 1 diabetes identified 3 candidate loci for diabetic nephropathy. In this study, we examined the association of the 3 single nucleotide polymorphism (SNP) loci with susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes.

Methods

We genotyped 3 SNPs, rs7583877 in AFF3, rs12437854 in the RGMA-MCTP2 locus and rs7588550 in ERBB4, for 2,300 Japanese patients with type 2 diabetes [initial study, 1,055 nephropathy cases with overt proteinuria or with end-stage renal disease (ESRD) and 1,245 control patients with normoalbuminuria]. The association of these SNPs with diabetic nephropathy was examined by using a logistic regression analysis.

Results

We observed a significant association of rs7588550 in ERBB4 with diabetic nephropathy in the Japanese patients with type 2 diabetes, although the effect direction was not consistent with that in the European study [p = 0.0126, odds ratio (OR) = 0.79, 95 % confidence interval (CI): 0.65–0.95]. We further examined the association of rs7588550 with diabetic nephropathy in an independent Japanese cohort (596 nephropathy cases and 311 controls) and observed the same trend of the association with the initial study. We did not observe any association of the remaining 2 SNP loci with diabetic nephropathy in the present Japanese sample.

Conclusion

The association of SNP loci derived from GWAS in European type 1 diabetes with diabetic nephropathy was not replicated in the Japanese patients with type 2 diabetes, although the ERBB4 locus may have some effect also in Japanese type 2 diabetes.

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Acknowledgments

We thank the technical staff of the Laboratory for Endocrinology and Metabolism at RIKEN Center for Genomic Medicine for their technical assistances. This work was partly supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to S.M.).

Conflict of interest

All the authors have declared no competing interest.

Author information

Authors and Affiliations

  1. Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan

    Shiro Maeda, Minako Imamura & Mahiro Kurashige

  2. Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Mahiro Kurashige, Kazushige Hanaoka & Tatsuo Hosoya

  3. Department of Medicine, Shiga University of Medical Science, Otsu, Japan

    Shinichi Araki, Takashi Uzu & Hiroshi Maegawa

  4. Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan

    Daisuke Suzuki, Tomoya Umezono & Masao Toyoda

  5. Diabetes Center, Tokyo Women’s Medical University, Tokyo, Japan

    Tetsuya Babazono & Yasuko Uchigata

  6. Kawai Clinic, Tsukuba, Japan

    Koichi Kawai

  7. Department of Internal Medicine, Osaka City General Hospital, Osaka, Japan

    Masahito Imanishi

Authors
  1. Shiro Maeda
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  2. Minako Imamura
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  3. Mahiro Kurashige
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  4. Shinichi Araki
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  7. Takashi Uzu
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  9. Masao Toyoda
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  15. Tatsuo Hosoya
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Corresponding author

Correspondence to Shiro Maeda.

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Maeda, S., Imamura, M., Kurashige, M. et al. Replication study for the association of 3 SNP loci identified in a genome-wide association study for diabetic nephropathy in European type 1 diabetes with diabetic nephropathy in Japanese patients with type 2 diabetes. Clin Exp Nephrol 17, 866–871 (2013). https://doi.org/10.1007/s10157-013-0797-5

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  • DOI: https://doi.org/10.1007/s10157-013-0797-5

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