摘要
目的探索Notch通路的配体JAG1和限速酶ADAM10和ADAM17与先天性心脏病(congenital heart disease,CHD)发病的相关性。方法选取来自山东、上海两地的1 053例CHD患者血液样本和1 000例对照样本,对这3个基因的5′启动子区和3′-UTR区进行了全测序,并进行统计分析及简要功能验证。结果检测到7个SNP(含2个新发SNP位点Ch2:9695908T/C和Ch20:10655928T/C)和1个单倍型组合具有显著性频率差异。双荧光素酶报告基因试验表明其中ADAM17启动子区的rs3811592Mrs13415726Mrs3811591M这个连锁单倍型可显著下调基因表达;而JAG1启动子区的rs7264849M则可显著上调基因表达。结论这些SNP突变可能影响Notch信号的强弱,从而与心脏发育异常相关。
Objective To study the relationship between Notch ligand JAG1, rate-limiting enzymes ADAM） and ADAM17 and congenital heart disease （CHD）. Methods We sequenced those three genes＇ promotor region and 3＇-UTR region in I （153 CHD cases and l 000 controls from Shanghai and Shandong Province. Statistical analysis and brief functional verification were made. Results We found 7 SNPs and 1 Haplotype in the non-coding region which were significantly higher in frequency in cases than in controls （P^（）. 0（11）I ）. Dual-luciferase assay proved that the rs3811592M^ rs13415726M^ rs3811591 M^ and haplotype in the promoter region of ADAM17 could significantly down regulate the gene expression, while the SNP rs7264849M in regulate the gene expression, which in turn the promoter region of JAG1 could significantly up- can contribute to abnormal heart decelopment.
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2014年第6期734-741,共8页
Fudan University Journal of Medical Sciences
基金
天津市卫生行业重点攻关项目(12KG116)
天津市自然科学基金(14JCYBJC25000)~~
