Haplotype analysis of the estrogen receptor 1 gene in male genital and reproductive abnormalities

Masanori Watanabe, Rie Yoshida, Katsuhiko Ueoka, Katsuya Aoki, Isoji Sasagawa, Tomonobu Hasegawa, Kou Sueoka, Naoyuki Kamatani, Yasunori Yoshimura, Tsutomu Ogata

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53 Citations (Scopus)


Background: We have recently suggested that homozygosity for a specific 'AGATA' haplotype within a ∼50 kb linkage disequilibrium (LD) block of the gene for estrogen receptor α (ESR1) may raise the susceptibility to cryptorchidism by enhancing estrogenic effects of environmental endocrine disruptors (EEDs). Methods: Haplotype analysis of ESR1 was performed in 328 Japanese subjects, i.e. 70 patients with micropenis (MP), 43 patients with hypospadias (HS), 80 patients with spermatogenic failure (SF) and 135 control males. Genotyping was performed by the 5′ nuclease assay. Results: The LD block was identified in each of the patient groups and in the control males. The frequency of homozygotes for the specific 'AGATA' haplotype was markedly higher in the HS patients [P = 0.0000033, odds ratio [OR] = 11.26] and slightly higher in the MP patients (P = 0.034, OR = 3.64) than in the control males, and the 'AGATA' haplotype was strongly associated with HS (P = 0.0000022, OR = 11.26) and weakly associated with MP (P = 0.040, OR = 3.64) in a recessive mode. There was no significant difference between the SF patients and the control males. Conclusions: Our results support the hypothesis that homozygosity for the specific ESR1 'AGATA' haplotype may increase the susceptibility to the development of male genital abnormalities in response to estrogenic EEDs.

Original languageEnglish
Pages (from-to)1279-1284
Number of pages6
JournalHuman Reproduction
Issue number5
Publication statusPublished - 2007 May


  • Environmental endocrine disruptors
  • Estrogen receptor 1
  • Haplotype analysis
  • Susceptibility
  • Undermasculinization

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology


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