title: Two functional sequence variants of the GATA6 gene promoter in patients with indirect inguinal hernia.
abstract: Inguinal hernia is a common surgical disease, majority of which are indirect inguinal hernia (IIH). A positive family history has indicated that genetic factors play important roles in the IIH development. To date, genetic causes and underlying mechanisms for inguinal hernia remain largely unknown. During the embryonic development, GATA transcription factor 6 (GATA6) plays an essential role. Mutations in GATA6 gene and changed GATA6 levels have been associated with human diseases. As GATA6 acts in a dosage-dependent manner, we speculated that changed GATA6 levels, resulting from DNA sequence variants (DSVs) within the gene regulatory regions, may mediate the IIH development. In this study, the GATA6 gene promoter was genetically and functionally analyzed in IIH patients and ethnic-matched controls. Eleven DNA sequence variants (DSVs), including four SNPs and seven new variants, within the GATA6 gene promoter were identified. Two heterozygous DSVs, g.22168361C>A and g.22169106C>T, were identified in two IIH patients, but in none of controls. In cultured human fibroblast, these DSVs significantly reduced the GATA6 gene promoter activities. In addition, three heterozygous DSVs were only found in three controls. Five DSVs, including four SNPs and one new variant, were found in both IIH patients and controls with similar frequencies. Therefore, the DSVs within the GATA6 gene promoter may contribute to the IIH development as a risk factor by changing the GATA6 levels.
authors.affiliation: Division of Interventional Therapy, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Yuangang
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Division of Oncology, Jining First People's Hospital, Jining, Shandong 272011, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Huang
authors.affiliation: Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Jining Medical University Affiliated Hospital, Jining Medical University, Jining, Shandong 272029, China.
authors.forename: Shuchao
authors.initials: S
authors.lastname: Pang
authors.affiliation: Division of Pediatric 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; Shandong Sino-US Cooperation Research Center for Translational Medicine, 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: D000293:Adolescent; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D050993:GATA6 Transcription Factor / Q000235:genetics*; D017930:Genes, Reporter; D006552:Hernia, Inguinal / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011401:Promoter Regions, Genetic
chemical_list: D017931:DNA Primers; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human
keywords: DNA sequence variants; GATA6; Genetics; Indirect inguinal hernia; Promoter