title: EVC gene polymorphisms and risks of isolated hypospadias - a preliminary study.
abstract: BACKGROUND
  Hypospadias has a complex etiology with both genetic and environmental factors contributing to the condition. Urogenital abnormalities including hypospadias, are found in 22% of cases with Ellis van Creveld syndrome (EvC). Mutations in the EVC gene can cause major and minor anomalies, which form phenotypes that partially overlap with those present in EvC. The aim of this study was to evaluate the association between nucleotide variants of the EVC gene and the risk of hypospadias.
  
  
  METHODS
  Four single nucleotide polymorphisms (SNPs) of the EVC gene (rs3774856, rs2302075, rs1383180, rs7680768) were taken under investigation in 96 patients with isolated hypospadias and 284 matched controls. Genotyping of all polymorphisms was carried out by PCR and followed by appropriate restriction enzyme digestion (PCR-RFLP).
  
  
  RESULTS
  Individuals homozygous for the SNP rs2302075 (p.Thr449Lys) showed an elevated risk for hypospadias. Haplotypes containing the rs2302075 variant also revealed modest associations with hypospadias, which did not survive multiple testing corrections. None of the other tested EVC polymorphisms displayed significant association with the risk of hypospadias, either in dominant or recessive inheritance models.
  
  
  CONCLUSIONS
  The results of this study suggest that polymorphic variants of the EVC gene do not substantially contribute to the risk of hypospadias based on our study population. However, further studies should help to clarify the relationship between polymorphisms of EVC and hypospadias.
authors.affiliation: Department of Pediatric Surgery, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kowal
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Adrianna
authors.initials: A
authors.lastname: Mostowska
authors.affiliation: Department of Pediatric Surgery, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Mydlak
authors.affiliation: Department of Pediatrics, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Bożena
authors.initials: B
authors.lastname: Eberdt-Gołąbek
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Matthew
authors.initials: M
authors.lastname: Misztal
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Jagodziński
authors.affiliation: Department of Pediatrics, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Kamil K
authors.initials: KK
authors.lastname: Hozyasz
keywords: Ellis-van Creveld syndrome; gene polymorphisms; hypospadias