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19–22 APRIL, 2017, BARCELONA, SPAIN
S1: BASIC RESEARCH 1
Moderators: Darius Bägli (Canada), Marco Castagnetti (Italy)
ESPU Meeting on Wednesday 19, April 2017, 13:30–14:55
13:30–13:33
S1-1 (PP)
ARE GATA4 GENE VARIANTS ASSOCIATED
WITH HYPOSPADIAS?
Matthieu PEYCELON
1
, Lea CARLIER
2
, Muriel HOUANG
3
, Georges AUDRY
4
,
Serge AMSELEM
2
, Alaa EL GHONEIMI
5
, Jean-Pierre SIFFROI
2
and Capucine HYON
2
1) Robert-Debré Hospital, AP-HP; Université Paris Diderot, Sorbonne Paris Cité; Inserm UMR_S933, Pediatric Surgery
and Urology, Paris Cedex 19, FRANCE - 2) Trousseau Hospital, AP-HP; Université Pierre et Marie Curie; Inserm
UMR_S933, Genetics, Paris Cedex 12, FRANCE - 3) Trousseau Hospital, AP-HP, Endocrinology Laboratory, Paris
Cedex 12, FRANCE - 4) Trousseau Hospital, AP-HP; Université Pierre et Marie Curie, Pediatric Surgery, Paris Cedex
12, FRANCE - 5) Robert-Debré Hospital, AP-HP; Université Paris Diderot, Sorbonne Paris Cité, Pediatric Surgery and
Urology, Paris Cedex 19, FRANCE
PURPOSE
Hypospadias is the most common malformation affecting male genitalia and its incidence is increas-
ing. Although the causes remain often unknown, endocrine, vascular, genetic and environmental
factors have been implicated. The genetic basis is probably underestimated. Human Chorionic
Gonadotrophin (hCG) secretion in first trimester of pregnancy stimulates fetal testosterone produc-
tion through GATA4 transcription and phosphorylation. The aim of this study was to investigate the
role of variations in GATA4 gene in patients with hypospadias.
MATERIAL AND METHODS
Sequencing of GATA4 gene was performed on DNA extracted from blood lymphocytes. Analyses
included 68 patients treated for hypospadias between 2010 and 2013. Statistical analysis: chi-
squared test.
RESULTS
Eleven known exonic and intronic variations were idnetified but no novel variant was found. Two
exonic SNPs lead to missense base substitution: c.1129A>G, p.Ser377Gly (rs3729856) and
c.1138G>A, pVal380Met (rs114868912). Allele frequencies of six SNPSs (c.462C>T (rs56348550),
c.669G>A (rs55788387), c.723C>T (rs1062215), c.1056C>T (rs3729855), c.1129A>G (rs3729856)
and c.1146+45G>A (rs776215655)) were 0.73%, 0.73%, 0.73%, 1.47%, 16.2% and 0.73% respec-
tively in the hypospadias patients, significantly higher than 0.04%, 0.1%, 0.1%, 0.0008%, 4.3% and
0.0025% in the normal controls (p<0.05).
CONCLUSIONS
Mutations in GATA4 gene is unlikely responsible for hypospadias in French children. However,
polymorphisms in GATA4 gene may be associated with hypospadias. Given the small number of
cases analyzed, further study of a larger number of patients is needed to allow a more thorough
investigation of GATA4 variability and to delineate the mechanism by which GATA4 contributes to
hypospadias.