Limits...
EVC gene polymorphisms and risks of isolated hypospadias - a preliminary study.

Kowal A, Mostowska A, Mydlak D, Eberdt-Gołąbek B, Misztal M, Jagodziński PP, Hozyasz KK - Cent European J Urol (2015)

Bottom Line: Urogenital abnormalities including hypospadias, are found in 22% of cases with Ellis van Creveld syndrome (EvC).Genotyping of all polymorphisms was carried out by PCR and followed by appropriate restriction enzyme digestion (PCR-RFLP).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Surgery, Institute of Mother and Child, Warsaw, Poland.

ABSTRACT

Introduction: 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.

Material and 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.

No MeSH data available.


Related in: MedlinePlus

The Linkage Disequilibrium (LD) plot of HapMap SNPs within the EVC region. The plot was generated using the genotype data from HapMap CEU samples and the Haploview 4.0 software (Broad Institute, Cambridge, MA). The names of the tested SNPs are enclosed in boxes. The numbers in the squares indicate percentage of LD between a given pair of SNPs (D’ values).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526603&req=5

Figure 0001: The Linkage Disequilibrium (LD) plot of HapMap SNPs within the EVC region. The plot was generated using the genotype data from HapMap CEU samples and the Haploview 4.0 software (Broad Institute, Cambridge, MA). The names of the tested SNPs are enclosed in boxes. The numbers in the squares indicate percentage of LD between a given pair of SNPs (D’ values).

Mentions: Genomic DNA was isolated from peripheral blood lymphocytes by a salt-out extraction procedure. SNPs in the EVC gene were identified from the HapMap Genome Browser (http://hapmap.ncbi.nlm.nih.gov/), the NCBI dbSNP database (http://www.ncbi.nlm.nih.gov/projects/SNP/) and related literature. A final set of 4 SNPs was selected based on a minor allele frequency (MAF) over 15% in the Caucasian population and the EVC gene-linkage disequilibrium (LD) pattern. Characteristics of SNPs that were finally selected are presented in Table 1. The LD pattern and the structure of the haplotype blocks across the EVC gene were determined using genotype data from the HapMap database and Haploview 4.0 software (http://www.broad.mit.edu/mpg/haploview/). The plot of the pairwise LD between SNPs in the EVC gene is presented in Figure 1.


EVC gene polymorphisms and risks of isolated hypospadias - a preliminary study.

Kowal A, Mostowska A, Mydlak D, Eberdt-Gołąbek B, Misztal M, Jagodziński PP, Hozyasz KK - Cent European J Urol (2015)

The Linkage Disequilibrium (LD) plot of HapMap SNPs within the EVC region. The plot was generated using the genotype data from HapMap CEU samples and the Haploview 4.0 software (Broad Institute, Cambridge, MA). The names of the tested SNPs are enclosed in boxes. The numbers in the squares indicate percentage of LD between a given pair of SNPs (D’ values).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526603&req=5

Figure 0001: The Linkage Disequilibrium (LD) plot of HapMap SNPs within the EVC region. The plot was generated using the genotype data from HapMap CEU samples and the Haploview 4.0 software (Broad Institute, Cambridge, MA). The names of the tested SNPs are enclosed in boxes. The numbers in the squares indicate percentage of LD between a given pair of SNPs (D’ values).
Mentions: Genomic DNA was isolated from peripheral blood lymphocytes by a salt-out extraction procedure. SNPs in the EVC gene were identified from the HapMap Genome Browser (http://hapmap.ncbi.nlm.nih.gov/), the NCBI dbSNP database (http://www.ncbi.nlm.nih.gov/projects/SNP/) and related literature. A final set of 4 SNPs was selected based on a minor allele frequency (MAF) over 15% in the Caucasian population and the EVC gene-linkage disequilibrium (LD) pattern. Characteristics of SNPs that were finally selected are presented in Table 1. The LD pattern and the structure of the haplotype blocks across the EVC gene were determined using genotype data from the HapMap database and Haploview 4.0 software (http://www.broad.mit.edu/mpg/haploview/). The plot of the pairwise LD between SNPs in the EVC gene is presented in Figure 1.

Bottom Line: Urogenital abnormalities including hypospadias, are found in 22% of cases with Ellis van Creveld syndrome (EvC).Genotyping of all polymorphisms was carried out by PCR and followed by appropriate restriction enzyme digestion (PCR-RFLP).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Surgery, Institute of Mother and Child, Warsaw, Poland.

ABSTRACT

Introduction: 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.

Material and 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.

No MeSH data available.


Related in: MedlinePlus