Genome-wide DNA methylation profiling of CpG Islands in hypospadias

Shweta Choudhry, Archana Deshpande, Liang Qiao, Kenneth Beckman, Saunak Sen, Laurence S. Baskin

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Purpose: Hypospadias is one of the most frequent genital malformations in the male newborn, and results from abnormal penile and urethral development. The etiology of hypospadias remains largely unknown despite intensive investigations. Fetal androgens have a crucial role in genital differentiation. Recent studies have suggested that molecular mechanisms that underlie the effects of androgens on the fetus may involve disruption of epigenetic programming of gene expression during development. We assessed whether epigenetic modification of DNA methylation is associated with hypospadias in a case-control study of 12 hypospadias and 8 control subjects. Materials and Methods: Genome-wide DNA methylation profiling was performed on the study subjects using the Illumina Infinium® HumanMethylation450 BeadChip, which enables the direct investigation of methylation status of more than 485,000 individual CpG sites throughout the genome. The methylation level at each CpG site was compared between cases and controls using the t test and logistic regression. Results: We identified 14 CpG sites that were associated with hypospadias with p <0.00001. These CpG sites were in or near the SCARB1, MYBPH, SORBS1, LAMA4, HOXD11, MYO1D, EGFL7, C10orf41, LMAN1L and SULF1 genes. Two CpG sites in SCARB1 and MYBPH genes remained statistically significant after correction for multiple testing (p = 2.61×10 -09 , p corrected = 0.008; p = 3.06×10 -08 , p corrected = 0.02, respectively). Conclusions: To our knowledge this is the first study to investigate hypospadias using a unique and novel epigenetic approach. Our findings suggest DNA methylation patterns are useful in identifying new genes such as SCARB1 and MYBPH that may be involved in the etiology of hypospadias.

Original languageEnglish (US)
Pages (from-to)1450-1456
Number of pages7
JournalJournal of Urology
Volume188
Issue number4 SUPPL.
DOIs
StatePublished - Jan 1 2012

Fingerprint

Hypospadias
CpG Islands
DNA Fingerprinting
DNA Methylation
Genome
Epigenomics
Methylation
Androgens
Genes
Case-Control Studies
Fetus
Logistic Models
Gene Expression

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Choudhry, S., Deshpande, A., Qiao, L., Beckman, K., Sen, S., & Baskin, L. S. (2012). Genome-wide DNA methylation profiling of CpG Islands in hypospadias. Journal of Urology, 188(4 SUPPL.), 1450-1456. https://doi.org/10.1016/j.juro.2012.03.047

Genome-wide DNA methylation profiling of CpG Islands in hypospadias. / Choudhry, Shweta; Deshpande, Archana; Qiao, Liang; Beckman, Kenneth; Sen, Saunak; Baskin, Laurence S.

In: Journal of Urology, Vol. 188, No. 4 SUPPL., 01.01.2012, p. 1450-1456.

Research output: Contribution to journalArticle

Choudhry, S, Deshpande, A, Qiao, L, Beckman, K, Sen, S & Baskin, LS 2012, 'Genome-wide DNA methylation profiling of CpG Islands in hypospadias', Journal of Urology, vol. 188, no. 4 SUPPL., pp. 1450-1456. https://doi.org/10.1016/j.juro.2012.03.047
Choudhry S, Deshpande A, Qiao L, Beckman K, Sen S, Baskin LS. Genome-wide DNA methylation profiling of CpG Islands in hypospadias. Journal of Urology. 2012 Jan 1;188(4 SUPPL.):1450-1456. https://doi.org/10.1016/j.juro.2012.03.047
Choudhry, Shweta ; Deshpande, Archana ; Qiao, Liang ; Beckman, Kenneth ; Sen, Saunak ; Baskin, Laurence S. / Genome-wide DNA methylation profiling of CpG Islands in hypospadias. In: Journal of Urology. 2012 ; Vol. 188, No. 4 SUPPL. pp. 1450-1456.
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