Hypospadias and genes related to genital tubercle and early urethral development

Details

• Alternative Title:
  J Urol
• Personal Author:
  Carmichael, Suzan L. ; Ma, Chen ; Choudhry, Shweta ; Lammer, Edward J. ; Witte, John S. ; Shaw, Gary M.
• Description:
  Purpose
  
  We determined whether variants in genes associated with genital tubercle (the anlage for the penis) and early urethral development were associated with hypospadias in humans.
  
  Materials and Methods
  
  We examined 293 relatively common tagSNPs in BMP4, BMP7, FGF8, FGF10, FGFR2, HOXA13, HOXD13, HOXA4, HOXB6, SRY, WT1, WTAP, SHH, GLI1, GLI2, and GLI3. The analysis included 624 cases (81 mild, 319 moderate, 209 severe, 15 undetermined severity) and 844 population-based non-malformed male controls born in California from 1990-2003.
  
  Results
  
  There were 28 SNPs for which any of the comparisons (i.e., overall or for a specific severity) had a p-value <0.01. The homozygous variant genotypes for four SNPs in BMP7 were associated with at least 2-fold increased risk of hypospadias, regardless of severity. Five SNPs for FGF10 were associated with 3- to 4-fold increased risks, regardless of severity; for four of them, results were restricted to whites. For GLI1, GLI2 and GLI3, there were 12 associated SNPs but results were inconsistent by severity and race-ethnicity. For SHH, one SNP was associated with 2.4-fold increased risk of moderate hypospadias. For WT1, six SNPs were associated with approximately 2-fold increased risks, primarily for severe hypospadias.
  
  Conclusions
  
  This study provides evidence that SNPs in several genes that contribute to genital tubercle and early urethral development are associated with hypospadias risk.
  
  
• Subjects:
  Case-Control Studies Humans Hypospadias Infant, Newborn Male Penis Polymorphism, Single Nucleotide Severity Of Illness Index Urethra
• Keywords:
  Genes Genital Tubercle Hypospadias
• Source:
  J Urol. 190(5):1884-1892
• Pubmed ID:
  23727413
• Pubmed Central ID:
  PMC4103581
• Document Type:
  Journal Article
• Funding:
  R01 ES017060/ES/NIEHS NIH HHSUnited States/ ; U01 DD000489/DD/NCBDD CDC HHSUnited States/ ; 6U01DD000489/DD/NCBDD CDC HHSUnited States/
• Volume:
  190
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:1b04dbd8ff1513cbd3552eaba226fdaf524ca99e58a63290bf22460b359671ac
• Download URL:
  https://stacks.cdc.gov/view/cdc/30041/cdc_30041_DS1.pdf
• File Type:
  [PDF - 115.35 KB ]