Polymorphism of 3′ UTR of MAMLD1 gene is also associated with increased risk of isolated hypospadias in Indian children: a preliminary report

• Published in: Pediatric surgery international 2016-05, Vol.32 (5), p.515-524
• Main Authors: Ratan, Simmi K., Sharma, Anju, Kapoor, Seema, Polipalli, Sunil K., Dubey, Divya, Mishra, Tarun K., Sinha, Shandip K., Agarwal, Satish K.
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; Child; Child, Preschool; DNA-Binding Proteins - genetics; Humans; Hypospadias - blood; Hypospadias - genetics; Infant; Infant, Newborn; Luteinizing Hormone - blood; Male; Medicine; Medicine & Public Health; Mutation; Nuclear Proteins - genetics; Original Article; Pediatric Surgery; Pediatrics; Polymorphism, Genetic; Surgery; Testosterone - blood; Transcription Factors - genetics
• ISSN: 0179-0358; 1437-9813
• DOI: 10.1007/s00383-016-3856-7

Objective To study MAMLD1 gene polymorphisms, serum LH and testosterone levels amongst Indian children with isolated hypospadias (IH) and controls. Materials and 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. Conclusion 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.