International Urology and Nephrology

, Volume 45, Issue 6, pp 1613–1620 | Cite as

MTHFR, MTR and MTRR polymorphisms and risk of chronic kidney disease in Japanese: cross-sectional data from the J-MICC Study

  • Asahi HishidaEmail author
  • Rieko Okada
  • Yin Guang
  • Mariko Naito
  • Kenji Wakai
  • Satoyo Hosono
  • Kazuyo Nakamura
  • Tanvir Chowdhury Turin
  • Sadao Suzuki
  • Hideshi Niimura
  • Haruo Mikami
  • Jun Otonari
  • Nagato Kuriyama
  • Sakurako Katsuura
  • Michiaki Kubo
  • Hideo Tanaka
  • Nobuyuki Hamajima
Nephrology - Original Paper



Chronic kidney disease (CKD) is well known as a strong risk factor for both of end-stage renal disease and cardiovascular disease. To clarify the associations of MTHFR, MTR, and MTRR polymorphisms with the risk of CKD in Japanese, we examined this association among Japanese subjects using cross-sectional data.


The subjects for this analysis were 3,318 participants consecutively selected from the Japan Multi-institutional Collaborative Cohort (J-MICC) Study. The polymorphisms were genotyped by a multiplex polymerase chain reaction-based Invader assay. Age- and sex-adjusted odds ratio (aOR) of CKD with stage 3–5 was calculated for each genotype.


When those with MTHFR C677T C/C were defined as references, those with MTHFR C677T C/T and T/T demonstrated the aORs for CKD of 1.14 (95 % CI 0.93–1.40) and 1.39 (1.06–1.82), respectively. Marginally significantly decreased risk of CKD with increasing number of MTR A2756G G allele (p = 0.058) was observed. Stratified analyses by plasma folate low (<7.4 ng/ml) or high (≥7.4 ng/ml) suggested significantly higher OR of CKD for those with MTHFR C677T T/T and low serum folate with the aOR of 2.07 (95 % CI 1.30–3.31) compared with that for those with MTHFR C677T T/T and high serum folate.


The present study found a significant association between the subjects with the T/T genotype of MTHFR C677T polymorphism and the elevated risk of CKD, which may suggest the possibility of the risk evaluation and prevention of this potentially life-threatening disease based on genetic traits in the near future.


Chronic kidney disease Folate metabolism MTHFR Polymorphism Renal insufficiency 



The authors wish to thank Mr. Kyota Ashikawa and Ms. Tomomi Aoi at the Laboratory of Genotyping Development, Center for Genomic Medicine, RIKEN, for genotyping. The authors also thank Ms. Yoko Mitsuda and Ms. Keiko Shibata at Daiko Medical Center, Nagoya University, for their technical assistance. This study was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas of Cancer (No. 17015018) and Scientific Support Programs for Cancer Research, and Grant-in-Aid for Scientific Research on Innovative Areas (No. 221S0001) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

Conflict of interest



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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Asahi Hishida
    • 1
    Email author
  • Rieko Okada
    • 1
  • Yin Guang
    • 1
  • Mariko Naito
    • 1
  • Kenji Wakai
    • 1
  • Satoyo Hosono
    • 2
  • Kazuyo Nakamura
    • 3
  • Tanvir Chowdhury Turin
    • 4
    • 5
  • Sadao Suzuki
    • 6
  • Hideshi Niimura
    • 7
  • Haruo Mikami
    • 8
  • Jun Otonari
    • 9
  • Nagato Kuriyama
    • 10
  • Sakurako Katsuura
    • 11
  • Michiaki Kubo
    • 12
  • Hideo Tanaka
    • 2
  • Nobuyuki Hamajima
    • 13
  1. 1.Department of Preventive MedicineNagoya University Graduate School of MedicineShowa-ku, NagoyaJapan
  2. 2.Division of Epidemiology and PreventionAichi Cancer Center Research InstituteNagoyaJapan
  3. 3.St. Mary’s College Faculty of NursingKurumeJapan
  4. 4.Department of Health ScienceShiga University of Medical ScienceOtsuJapan
  5. 5.Department of MedicineUniversity of CalgaryCalgaryCanada
  6. 6.Department of Public HealthNagoya City University Graduate School of Medical SciencesNagoyaJapan
  7. 7.Department of International Island and Community MedicineKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
  8. 8.Division of EpidemiologyChiba Cancer Center Research InstituteChibaJapan
  9. 9.Department of Preventive MedicineKyushu University Graduate School of Medical SciencesFukuokaJapan
  10. 10.Department of Social Medicine and Cultural SciencesKyoto Prefectural University of MedicineKyotoJapan
  11. 11.Department of Preventive Medicine, Institute of Health BiosciencesThe University of Tokushima Graduate SchoolTokushimaJapan
  12. 12.Center for Genomic MedicineRIKENYokohamaJapan
  13. 13.Young Leaders’ ProgramNagoya University Graduate School of MedicineNagoyaJapan

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