Single-nucleotide and copy-number variance related to severity of hypospadias.
Pediatr Surg Int
; 34(9): 991-1008, 2018 Sep.
Article
en En
| MEDLINE
| ID: mdl-30078147
ABSTRACT
BACKGROUND:
The genetic association of hypospadias-risk studies has been conducted in Caucasians, Chinese-Han populations and few in Indian populations. However, no comprehensive approach has been followed to assess genetic involvement in the severity of the disorder.METHODS:
The study evaluated to establish the correlation between genotyped single nucleotide and copy number variants (SNPs/CNVs) and severity of hypospadias by an association in a total 30 SNPs in genes related to sex hormone-biosynthesis and metabolism; embryonic-development and phospholipase-D-signalling pathways on 138 surgery-confirmed hypospadias-cases from North India (84 penile and 28 cases of penoscrotal-hypospadias as compared with 31 cases of glanular + coronal), and analyzed and identified CNVs in four familial cases (18 members) and three paired-sporadic cases (6 members) using array-based comparative-genomic-hybridization and validated in 32 hypospadias samples by TaqMan assay.RESULTS:
Based on odds ratio at 95% CI, Z Statistic and Significance Levels, STS gene-rs17268974 was associated with Penile-Hypospadias and 9-SNPs [seven-SNPs (rs5934740; rs5934842; rs5934913; rs6639811; rs3923341; rs17268974; rs5934937)] of STS gene; rs7562326-SRD5A2 and rs1877031-STARD3 were associated with penoscrotal-hypospadias. On aggregate analysis with p < 0.001, we identified homozygous-loss of Ch7q34 (PRSS3P2, PRSS2). On validation in previously CNV-characterized and new (32 hypospadias cases), we identified PRSS3P2-loss in most of the grade 3 and 4 hypospadias. Hence, Grade 1 and 2 (coronal and granular) show no-PRSS3P2-loss and no-association with SNPs in STS; SRD5A2; STARD3-gene but Grade 3 and 4 (Penile and Penoscrotal) show PRSS3P2-loss accompanied with the association of SNPs in STS; SRD5A2; STARD3.CONCLUSIONS:
Hence, homozygous-loss of PRSS3P2 accompanied with the association of STS; SRD5A2; STARD3 may link to the severity of the disease.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Índice de Severidad de la Enfermedad
/
Polimorfismo de Nucleótido Simple
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Variaciones en el Número de Copia de ADN
/
Hipospadias
Límite:
Humans
/
Male
Idioma:
En
Revista:
Pediatr Surg Int
Asunto de la revista:
PEDIATRIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
India