title: Polymorphism of 3' UTR of MAMLD1 gene is also associated with increased risk of isolated hypospadias in Indian children: a preliminary report.
abstract: OBJECTIVE
  To study MAMLD1 gene polymorphisms, serum LH and testosterone levels amongst Indian children with isolated hypospadias (IH) and controls.
  
  
  METHODS
  Screening of the MAMLD1 gene was performed by PCR sequencing method in 100 Indian children aged 0-12 years presenting with IH and 100 controls. LH and testosterone hormone levels were also assessed (categorized in four age-wise groups).
  
  
  RESULTS
  IH subjects had significantly higher incidence of MAMLD1 polymorphism as compared to controls (33 vs 15 %, p = 0.01). Of various genomic variants identified in this study, the noteworthy novel ones were missense mutation P299A and single nucleotide polymorphism c.2960C>T in 3' UTR of Exon 7. While p 299A was found to cause protein structural instability consequent to amino acid change, eighty percent subjects with c.2960C>T in 3' UTR of Exon 7 (corresponding to newly discovered currently non-validated exon 11) were found to have lower testosterone levels when compared with their age group mean. IH showed statistically higher incidence of c.2960C>T in comparison to controls (22 vs 10 %, p value 0.046) and about 2.5-folds higher risk of this anomaly.
  
  
  CONCLUSIONS
  Occurrence of MAMDL1 gene polymorphisms, specially of c.2960C>T in 3' UTR of its exon 7 is associated with a higher risk of IH in Indian children, probably by lowering androgenic levels.
authors.affiliation: Department of Pediatric Surgery, Maulana Azad Medical College and Associated LokNayak Hospital, G-8/6, Second Floor, Malviya Nagar, New Delhi, 110017, India. drjohnsimmi@yahoo.com.
authors.forename: Simmi K
authors.initials: SK
authors.lastname: Ratan
authors.affiliation: Department of Biochemistry, Maulana Azad Medical College and Associated LokNayak Hospital, New Delhi, India.
authors.forename: Anju
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Pediatrics, Maulana Azad Medical College and Associated LokNayak Hospital, New Delhi, India.
authors.forename: Seema
authors.initials: S
authors.lastname: Kapoor
authors.affiliation: Department of Biochemistry, Maulana Azad Medical College and Associated LokNayak Hospital, New Delhi, India.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Polipalli
authors.affiliation: Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Dubey
authors.affiliation: Department of Biochemistry, Maulana Azad Medical College and Associated LokNayak Hospital, New Delhi, India.
authors.forename: Tarun K
authors.initials: TK
authors.lastname: Mishra
authors.affiliation: Department of Pediatric Surgery, Maulana Azad Medical College and Associated LokNayak Hospital, G-8/6, Second Floor, Malviya Nagar, New Delhi, 110017, India.
authors.forename: Shandip K
authors.initials: SK
authors.lastname: Sinha
authors.affiliation: Department of Pediatric Surgery, Maulana Azad Medical College and Associated LokNayak Hospital, G-8/6, Second Floor, Malviya Nagar, New Delhi, 110017, India.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Agarwal
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D007021:Hypospadias / Q000097:blood / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D013739:Testosterone / Q000097:blood; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C528016:MAMLD1 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D013739:Testosterone; D007986:Luteinizing Hormone
keywords: 3′ UTR; India; Isolated hypospadias; MAMLD1; Polymorphism
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