Identification and functional study of GATA4 gene regulatory variants in atrial septal defects

BMC Cardiovascular Disorders

Shuchao Pang¹  Bo Yan²  Jing Chen³  Jiping Shan⁴  Qianjin Cheng⁵  Dongchen Fan⁶ 

[1] Center for Molecular Genetics of Cardiovascular Diseases, Affiliated Hospital of Jining Medical University, Jining Medical University, 272100, Jining, Shandong, China;Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, 272100, Jining, Shandong, China;Shandong Provincial Sino-US Cooperation Research Center for Translational Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, 272100, Jining, Shandong, China;Center for Molecular Genetics of Cardiovascular Diseases, Affiliated Hospital of Jining Medical University, Jining Medical University, 272100, Jining, Shandong, China;Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, 272100, Jining, Shandong, China;Shandong Provincial Sino-US Cooperation Research Center for Translational Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, 272100, Jining, Shandong, China;Center for Molecular Medicine, Yanzhou People’s Hospital, 272100, Jining, Shandong, China;Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, 272029, Jining, Shandong, China;Department of Medicine, Shandong University School of Medicine, 250012, Jinan, Shandong, China;Division of Cardiac Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, 272100, Jining, Shandong, China;Division of Cardiac Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, 272100, Jining, Shandong, China;Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, 272029, Jining, Shandong, China;Division of Medical Ultrasonics, Affiliated Hospital of Jining Medical University, Jining Medical University, 272100, Jining, Shandong, China;

关键词: Atrial septal defects;    Genetics;    GATA4;    Promoter;    Regulatory variants;   

DOI  :  10.1186/s12872-021-02136-w

来源: Springer

【 摘 要 】

BackgroundCongenital heart disease (CHD) is the leading cause of mortality from birth defects. In adult CHD patients with successful surgical repair, cardiac complications including heart failure develop at late stage, likely due to genetic causes. To date, many mutations in cardiac developmental genes have been associated with CHD. Recently, regulatory variants in genes have been linked to many human diseases. Although mutations and splicing variants in GATA4 gene have been reported in CHD patients, few regulatory variants of GATA4 gene are identified in CHD patients.MethodsGATA4 gene regulatory region was investigated in the patients with atrial septal defects (ASD) (n = 332) and ethnic-matched controls (n = 336).ResultsFive heterozygous regulatory variants including four SNPs [g.31360 T>C (rs372004083), g.31436G>A, g.31437C>A (rs769262495), g.31487C>G (rs1053351749) and g.31856C>T (rs1385460518)] were only identified in ASD patients. Functional analysis indicated that the regulatory variants significantly affected the transcriptional activity of GATA4 gene promoter. Furthermore, two of the five regulatory variants have evidently effected on transcription factor binding sites.ConclusionsOur data suggested that GATA4 gene regulatory variants may confer ASD susceptibility by decreasing GATA4 levels.

【 授权许可】

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