IntroductionOf interest is if factors like maternal diet can influence the risk of hypospadias–affected pregnancy. Increased propionylcarnitine (C3) is regarded as a biomarker of vitamin B12 deficiency. The retrospective study was undertaken to determine whether increased propionylcarnitine and low methionine in newborns are associated with hypospadias.Material and methods41 newborns with hypospadias and 90 control newborns without congenital anomalies were investigated. Whole blood propionylcarnitine and methionine concentrations were measured using tandem mass spectrometry.ResultsThe mean concentration of propionylcarnitine was higher in newborns with hypospadias compared with newborns without congenital anomalies (p = 0.026). The mean methionine level in cases was insignificantly lower than in controls.ConclusionThere appears to be an association between decreased vitamin B12, as indexed by an increase of propionylcarnitine, and hypospadias in the investigated group of patients.

IntroductionHypospadias 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.Material and methodsFour 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).ResultsIndividuals 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.ConclusionsThe 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.

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Background: Hypospadias (HS) is one of the most common congenital malformations. Complications of corrective surgery in HS correlate with patients’ opinions on their voiding ability and sexual life as adults. Etiology of HS involves both genetic and environmental factors. GCH1, which belongs to recently identified urothelial genes influencing voiding behavior, encodes rate-limiting enzyme catalyzing the production of tetrahydrobiopterin (BH4). A requirement for BH4, a metabolite structurally related to folic acid and riboflavin, in embryonic development was reported. Objectives: The aim of the present study was to investigate the association of selected polymorphic variants of BH4 pathway genes with hypospadias. Methods: We performed an analysis of 6 SNPs of GCH1, PAH and AGMO-DGKB loci in a group of 166 boys with isolated hypospadias and a properly matched control group. Results: There was no evidence for either allelic or genotypic association with the risk of HS for the tested nucleotide variants (rs12425434, rs7485331, rs17128050, rs8004018, rs17128077, rs2191349). The lack of association with single SNPs was confirmed at the haplotype level. The exhaustive multifactor dimensionality reduction (MDR) analysis revealed no significant interactive effect of polymorphic variants of BH4 pathway genes on HS susceptibility. Conclusions: The presented results did not support an association between SNPs of GCH1 and PAH and the risk of HS.