title: Genetic analysis of the TBX1 gene promoter in indirect inguinal hernia.
abstract: Inguinal hernia is a common disease, most cases of which are indirect inguinal hernia (IIH). Genetic factors play an important role for inguinal hernia. Increased incidences of inguinal hernia have been reported in patients with 22q11.2 microdeletion syndrome, which is mainly caused by TBX1 gene mutations. Thus, we hypothesized that altered TBX1 gene expression may contribute to IIH development. In this study, the human TBX1 gene promoter was genetically analyzed in children with IIH (n=100) and ethnic-matched controls (n=167). Functions of DNA sequence variants (DSVs) within the TBX1 gene promoter were examined in cultured human fibroblast cells. The results showed that two heterozygous DSVs were found, both of which were single nucleotide polymorphisms. One DSV, g.4248 C>T (rs41298629), was identified in a 2-year-old boy with right-sided IIH, but not in all controls, which significantly decreased TBX1 gene promoter activity. Another DSV, g.4199 C>T (rs41260844), was found in both IIH patients and controls with similar frequencies (P>0.05), which did not affect TBX1 gene promoter activity. Collectively, our data suggested that the DSV within the TBX1 gene promoter may change TBX1 level, contributing to IIH development as a rare risk factor. Underlying molecular mechanisms need to be established.
authors.affiliation: Division of General Surgery, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of General Surgery, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Qingluan
authors.initials: Q
authors.lastname: Han
authors.affiliation: Division of Electrocardiogram, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of General Surgery, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Division of General Surgery, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Hongjin
authors.initials: H
authors.lastname: Fan
authors.affiliation: Division of General Surgery, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Qining
authors.initials: Q
authors.lastname: Xing
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China. Electronic address: yanbo@mail.jnmc.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006552:Hernia, Inguinal / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins; C108625:TBX1 protein, human
keywords: DNA sequence variants; DSV; DSVs; FGF10; FGF8; FoxA2; Genetics; IIH; Indirect inguinal hernia; Pitx2; Promoter; SNPs; T-box transcription factor 1; TBX1; fibroblast growth factor 10; fibroblast growth factor 8; forkhead box factor A2; indirect inguinal hernia; paired-like homeodomain factor 2; single nucleotide polymorphisms