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Functional variant in microRNA‐196a2 contributes to the susceptibility of congenital heart disease in a Chinese population
Author(s) -
Xu Jing,
Hu Zhibin,
Xu ZhengFeng,
Gu Haiyong,
Yi Long,
Cao Hailong,
Chen Jiaping,
Tian Tian,
Liang Jie,
Lin Ying,
Qiu Wanshan,
Ma Hongxia,
Shen Hongbing,
Chen Yijiang
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21044
Subject(s) - biology , microrna , hox gene , genetics , single nucleotide polymorphism , genotyping , genotype , phenotype , gene , bioinformatics , gene expression
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 =6.81×10 −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. Hum Mutat 30:1–6, 2009. © 2009 Wiley‐Liss, Inc.