A TBX5 3′UTR variant increases the risk of congenital heart disease in the Han Chinese population

• DOI: 10.1038/celldisc.2017.26
• Publication Date: 2017-07-26T13:17:02Z
• Authors: Feng Wang; Dong Liu; Ran-Ran Zhang; Li-Wei Yu; Jian-Yuan Zhao; Xue-Yan Yang; Song-Shan Jiang; Duan Ma; Bin Qiao; Feng Zhang; Li Jin; Yong-Hao Gui; Hong-Yan Wang
• Keywords: 0301 basic medicine; 03 medical and health sciences; Article; 3. Good health

Abstract TBX5 is a vital transcription factor involved in cardiac development dosage-dependent manner. But little known about the potential association of 3′ untranslated region (UTR) variations with congenital malformations. This study aimed to investigate relationship between 3′UTR variants and risk for heart disease (CHD) susceptibility two Han Chinese populations, reveal its molecular mechanism. The CHD was examined 1 177 patients 990 healthy controls independent case–control studies. Variant rs6489956 C>T found be associated increased both cohorts. combined CT TT genotype carriers 1.83 times higher than that CC genotype, while or 1.94 2.31 carriers, respectively. Quantitative real-time PCR western blot analysis showed T allele exhibited reduced mRNA protein levels CHDs tissues. Compared C allele, binding affinity miR-9 miR-30a luciferase assays surface plasmon resonance analysis. Functional confirmed downregulated expression at transcriptional translational levels, zebrafish model were support interaction miR-9/30a (C allele). We concluded variant population because it changes target miRNAs specifically mediate expression.