title: Functional variant in microRNA-196a2 contributes to the susceptibility of congenital heart disease in a Chinese population.
abstract: Hox gene clusters play an important role during cardiac septation to valve formation in different species, and the miR-196a-HOXB8-Sonic hedgehog signaling pathway is of particular interest. Recently, we found that a genetic variant of rs11614913 in the miR-196a2 sequence could alter mature miR-196a expression and target mRNA binding; this observation led us to hypothesize that rs11614913 might influence susceptibility to sporadic congenital heart disease (CHD). We conducted a three-stage case-control study of CHD in Chinese to test our hypothesis by genotyping miR-196a2 rs11614913 and three other pre-miRNA SNPs (miR-146a rs2910164, miR-149 rs2292832, and miR-499 rs3746444) in 1,324 CHD cases and 1,783 non-CHD controls. We found that rs11614913 CC was associated with a significantly increased risk of CHD in all three stages combined (P=6.81 x 10(-6)). In a genotype-phenotype correlation analysis using 29 cardiac tissue samples of CHD, rs11614913 CC was associated with significantly increased mature miR-196a expression (P=0.001). In vitro binding assays further revealed that the rs11614913 variant affects HOXB8 binding to mature miR-196a. This is the first study to indicate that miR-196a2 rs11614913 plays a role in sporadic CHD susceptibility.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Zhengfeng
authors.initials: Z
authors.lastname: Xu
authors.forename: Haiyong
authors.initials: H
authors.lastname: Gu
authors.forename: Long
authors.initials: L
authors.lastname: Yi
authors.forename: Hailong
authors.initials: H
authors.lastname: Cao
authors.forename: Jiaping
authors.initials: J
authors.lastname: Chen
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.forename: Wanshan
authors.initials: W
authors.lastname: Qiu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Yijiang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002681:China; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C542543:MIRN196 microRNA, human; D035683:MicroRNAs