stratification after validation in other LQTS populations.using a family-based association analysis. NOS1AP variants were significantly associated with the
occurrence of symptoms (rs4657139, p=0.019; rs16847548, p=0.003), with clinical severity as
manifested by a greater probability for cardiac arrest and sudden death (rs4657139, p=0.028;
rs16847548, p=0
论文范文http://www.chuibin.com/ .014), and with greater likelihood of having a QT interval in the top 40% of values本文来自优.文,论-文·网原文请找腾讯324,9114
among all mutation carriers (rs4657139, p=0.03; rs16847548, p=0.03).
Conclusions—These findings indicate that NOS1AP, a gene first identified as affecting the QTc
interval in a general population, also influences sudden death risk in subjects with LQTS. The
association of NOS1AP genetic variants with risk for life-threatening arrhythmias suggests that this
gene is a genetic modifier of LQTS and this knowledge may be clinically useful for risk-stratification
for patients with this disease, after validation in other LQTS populations.
Keywords
long-QT syndrome; nitric oxide synthase; KCNQ1; genetics; arrhythmiaIntroduction
The congenital long-QT syndrome (LQTS) is an inherited disorder of abnormal myocardial
1
repolarization in which there is a high risk for potentially lethal cardiac arrhythmias. The
disorder is caused by mutations in several genes most of which encode ion channel subunits
involved in the regulation of the cardiac action potential. The most common form of LQTS
(LQT1) is caused by mutations in KCNQ1, a gene encoding the pore-forming subunit of
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potassium channels responsible for the slow cardiac delayed rectifier current. In many
families, LQTS exhibits incomplete penetrance and variable expressivity, which suggest the
论文范文http://www.chuibin.com/ existence of factors other than the primary mutation that can modify the probability of
3-6
symptoms. Identification of genetic modifiers of LQTS would lead to improved risk
stratification among mutation carriers and could also provide information about the risk for
life-threatening arrhythmias in more common conditions, such as acute myocardial infarction
and congestive heart failure.
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