title: Mild decrease in TBX20 promoter activity is a potentially protective factor against congenital heart defects in the Han Chinese population.
abstract: Congenital heart defects (CHDs) are one of the most common human birth defects worldwide. TBX20 is a crucial transcription factor for the development of embryonic cardiovascular system. Previous studies have demonstrated that mutations in the TBX20 coding region contribute to familial and sporadic CHD occurrence. However, it remains largely unknown whether variants in the TBX20 regulatory region are also related to CHDs. In this study, we sequenced the 2 kb region upstream of the TBX20 transcription start site in 228 CHD patients and 292 controls in a Han Chinese population. Among the 8 single nucleotide polymorphisms (SNPs) identified, six SNPs are in strong linkage disequilibrium and the minor alleles are associated with lower CHD risk (for rs10235849 chosen as tag SNP, p = 0.0069, OR (95% CI) = 0.68 (0.51-0.90)). Functional analysis showed that the minor alleles have lower transcriptional activity than major alleles in both human heart tissues and three cell lines. The electrophoretic mobility shift assay suggested that TBX20 minor alleles may exhibit higher binding affinity with certain transcription repressors. Our results indicate that a moderately lower TBX20 activity potentially reduces CHD risk in the Han Chinese population, providing new insight in the study of CHD etiology.
authors.affiliation: Children's Hospital, Institute of Reproduction and Development. Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai, China.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Yu
authors.affiliation: Children's Hospital, Institute of Reproduction and Development. Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Genetic Engineering. MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Yang
authors.affiliation: Children's Hospital, Institute of Reproduction and Development. Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai, China.
authors.forename: Shu-Na
authors.initials: SN
authors.lastname: Sun
authors.affiliation: The State Key Laboratory of Genetic Engineering. MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Zheng
authors.affiliation: The State Key Laboratory of Genetic Engineering. MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Li
authors.affiliation: Children's Hospital, Institute of Reproduction and Development. Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai, China.
authors.forename: Yong-Hao
authors.initials: YH
authors.lastname: Gui
authors.affiliation: The State Key Laboratory of Genetic Engineering. MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D002460:Cell Line; D002681:China / Q000453:epidemiology; D004247:DNA / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006330:Heart Defects, Congenital / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D009687:Nuclear Proteins / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D009687:Nuclear Proteins; D020825:T-Box Domain Proteins; C420984:TBX20 protein, human; D004247:DNA