Journal of Assisted Reproduction and Genetics

, Volume 35, Issue 2, pp 257–263 | Cite as

Association of TUSC1 and DPF3 gene polymorphisms with male infertility

  • Youichi SatoEmail author
  • Chise Hasegawa
  • Atsushi Tajima
  • Shiari Nozawa
  • Miki Yoshiike
  • Eitetsue Koh
  • Jiro Kanaya
  • Mikio Namiki
  • Kiyomi Matsumiya
  • Akira Tsujimura
  • Kiyoshi Komatsu
  • Naoki Itoh
  • Jiro Eguchi
  • Aiko Yamauchi
  • Teruaki Iwamoto



Recently, genome-wide association studies of a Hutterite population in the USA revealed that five single nucleotide polymorphisms (SNPs) with a significant association with sperm quality and/or function in ethnically diverse men from Chicago were significantly correlated with family size. Of these, three SNPs (rs7867029, rs7174015, and rs12870438) were found to be significantly associated with the risk of azoospermia and/or oligozoospermia in a Japanese population. In this study, we investigated whether the rs10966811 (located in an intergenic region between the TUSC1 and IZUMO3 genes) and rs10129954 (located in the DPF3 gene) SNPs, previously related to family size, are associated with male infertility. In addition, we performed association analysis between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility.


We genotyped 145 patients with infertility (including 83 patients with azoospermia and 62 with oligozoospermia) and 713 fertile controls by PCR-RFLP technique for polymorphism. Because rs10966811 has no restriction sites, the SNP rs12376894 with strong linkage disequilibrium was selected as an alternative to rs10966811.


There was a statistically significant association between rs12376894 proxy SNP of rs10966811 and oligozoospermia. Also, a statistically significant association between rs10129954 and azoospermia, and oligozoospermia was observed. When we assessed the relationship between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility traits, we found that rs12348 in TUSC1 was significantly associated with azoospermia and oligozoospermia, but rs2772579 in IZUMO3 was not associated with male infertility.


We found that the polymorphisms in TUSC1 and DPF3 displayed strong associations with male infertility.


Single nucleotide polymorphism Male infertility Azoospermia Oligozoospermia Tumor suppressor candidate 1 Double plant homeodomain fingers Family 3 



We are grateful to the late Prof. Yutaka Nakahori for collecting blood samples from the participants.

Funding information

This study was supported in part by the Ministry of Health and Welfare of Japan (1013201) (to T.I.), Grant-in-Aids for Scientific Research (C) (26462461) (to Y.S.) from the Japan Society for the Promotion of Science, the European Union (BMH4-CT96-0314) (to T.I.), the Suzuki Urinary Foundation (to Y.S.), and a research program for the development of intelligent Tokushima artificial Exome (iTEX) from Tokushima University.

Compliance with ethical standards

This study was approved by the ethics committees of the University of Tokushima and St. Marianna Medical University. All participants provided written informed consent.

Conflict of interest

The authors declare that there are no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Youichi Sato
    • 1
    Email author
  • Chise Hasegawa
    • 1
  • Atsushi Tajima
    • 2
  • Shiari Nozawa
    • 3
  • Miki Yoshiike
    • 3
  • Eitetsue Koh
    • 4
  • Jiro Kanaya
    • 4
  • Mikio Namiki
    • 4
    • 5
  • Kiyomi Matsumiya
    • 6
  • Akira Tsujimura
    • 7
  • Kiyoshi Komatsu
    • 8
  • Naoki Itoh
    • 9
  • Jiro Eguchi
    • 10
  • Aiko Yamauchi
    • 1
  • Teruaki Iwamoto
    • 3
    • 11
  1. 1.Department of Pharmaceutical Information Science, Graduate School of Biomedical SciencesTokushima UniversityTokushimaJapan
  2. 2.Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical SciencesKanazawa UniversityKanazawaJapan
  3. 3.Department of UrologySt. Marianna University School of MedicineKawasakiJapan
  4. 4.Department of UrologyKanazawa University Graduate School of Medical SciencesKanazawaJapan
  5. 5.Department of UrologyHasegawa HospitalToyamaJapan
  6. 6.Department of UrologySuita Tokushukai HospitalOsakaJapan
  7. 7.Department of UrologyJuntendo University Urayasu HospitalUrayasuJapan
  8. 8.Department of UrologyHarasanshinkai HospitalFukuokaJapan
  9. 9.Department of UrologyNTT East Sapporo HospitalSapporoJapan
  10. 10.Department of UrologySasebo Kyosai HospitalSaseboJapan
  11. 11.Center for Infertility and IVFInternational University of Health and Welfare HospitalNasushiobaraJapan

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