A pilot study of the association between genetic polymorphisms involved in estrogen signaling and infant male genital phenotypes

Sheela Sathyanarayana, Shanna H. Swan, Federico M. Farin, Hui Wen Wilkerson, Michael Bamshad, Richard Grady, Chuan Zhou, Stephen M. Schwartz

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Single nucleotide polymorphisms (SNPs) in genes that influence development of the male reproductive tract have been associated with male genitourinary abnormalities. However, no studies have tested the relationship between SNPs and intermediate phenotypes such as anogenital distance (AGD), anoscrotal distance (ASD) and penile width (PW). We tested whether 24 common SNPs in eight genes that influence male genital development were associated with intermediate phenotypes in 106 healthy male infants from the Study for Future Families. We used DNA from buccal smears and linear regression models to assess the relationship between anogenital measurements and SNP genotypes with adjustment for covariates. We found that the rs2077647 G allele, located in the coding region of estrogen receptor alpha (ESR1), was associated with a shorter AGD (P0.02; 7.3 mm, 95% confidence interval (CI): 11.6 to 3.1), and the rs10475 T allele, located in the 3′ untranslated region of activating transcription factor 3 (ATF3), was associated with a shorter ASD (4.3mm, 95% CI: 7.2 to 1.4), although this result was not significant (P0.07) after controlling for multiple comparisons. We observed no association between PW and the SNPs tested. Minor alleles for two SNPs in genes that regulate estrogen signaling during male genital development were associated with AGD and ASD, although the significance of the association was marginal. Our findings suggestthat AGD and ASD are influenced by heritable factorsin genes known to be associated with frank male genital abnormalities such as hypospadias and cryptorchidism.

Original languageEnglish
Pages (from-to)766-772
Number of pages7
JournalAsian Journal of Andrology
Volume14
Issue number5
DOIs
StatePublished - Sep 2012

Keywords

  • gene
  • hypospadias
  • male
  • phenotype
  • polymorphism
  • reproductive

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