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首页> 美国卫生研究院文献>The Journal of Clinical Investigation >A common cardiac sodium channel variant associated with sudden infant death in African Americans SCN5A S1103Y
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A common cardiac sodium channel variant associated with sudden infant death in African Americans SCN5A S1103Y

机译：常见的心脏钠通道与婴儿猝死有关的变异在非裔美国人中SCN5A S1103Y

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Thousands die each year from sudden infant death syndrome (SIDS). Neither the cause nor basis for varied prevalence in different populations is understood. While 2 cases have been associated with mutations in type Vα, cardiac voltage-gated sodium channels (SCN5A), the “Back to Sleep” campaign has decreased SIDS prevalence, consistent with a role for environmental influences in disease pathogenesis. Here we studied SCN5A in African Americans. Three of 133 SIDS cases were homozygous for the variant S1103Y. Among controls, 120 of 1,056 were carriers of the heterozygous genotype, which was previously associated with increased risk for arrhythmia in adults. This suggests that infants with 2 copies of S1103Y have a 24-fold increased risk for SIDS. Variant Y1103 channels were found to operate normally under baseline conditions in vitro. As risk factors for SIDS include apnea and respiratory acidosis, Y1103 and wild-type channels were subjected to lowered intracellular pH. Only Y1103 channels gained abnormal function, demonstrating late reopenings suppressible by the drug mexiletine. The variant appeared to confer susceptibility to acidosis-induced arrhythmia, a gene-environment interaction. Overall, homozygous and rare heterozygous SCN5A missense variants were found in approximately 5% of cases. If our findings are replicated, prospective genetic testing of SIDS cases and screening with counseling for at-risk families warrant consideration.
机译：每年有数千人死于婴儿猝死综合症（SIDS）。既不了解不同人群中患病率高的原因也没有根据。尽管有2例病例与Vα型，心脏电压门控性钠离子通道（SCN5A）突变有关，但“重返睡眠”运动降低了SIDS患病率，与环境在疾病发病机理中的作用一致。在这里，我们研究了非洲裔美国人的SCN5A。 133个SIDS病例中有3个是S1103Y变异纯合子。在对照组中，1,056个中有120个是杂合基因型的携带者，以前与成人心律不齐的风险增加有关。这表明具有2个S1103Y拷贝的婴儿患SIDS的风险增加了24倍。发现变异的Y1103通道在体外基线条件下正常运行。由于SIDS的危险因素包括呼吸暂停和呼吸性酸中毒，因此Y1103和野生型通道的细胞内pH值降低。只有Y1103通道获得了异常功能，这表明美西律可抑制晚期重新开放。该变体似乎赋予了酸中毒诱发的心律不齐的易感性，一种基因与环境的相互作用。总体而言，在约5％的病例中发现了纯合子和稀有杂合子SCN5A错义变体。如果我们的发现得以重复，则应考虑对SIDS病例进行前瞻性基因测试并在高危家庭的咨询下进行筛查。

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