Makielski Jonathan C
Department of Medicine, Cardiovascular Medicine Section and Department of Physiology, University of Wisconsin, Madison, Wisconsin 53792, USA.
J Clin Invest. 2006 Feb;116(2):297-9. doi: 10.1172/JCI27689.
In this issue of the JCI, Bowers et al. show that the common polymorphism of the cardiac voltage-gated sodium channel, type Valpha (SCN5A), designated S1103Y, found in African Americans is associated with an increased risk of sudden infant death syndrome (SIDS). Wild-type and mutant SCN5A channels both functioned typically under normal conditions in vitro, but exposure to acidic intracellular pH levels such as those found in respiratory acidosis--a known risk factor for SIDS--produced abnormal gain-of-function late reopenings of S1103Y channels, behavior that is often associated with cardiac arrhythmias. These pathologic late reopenings were suppressed by low levels of the channel-blocking drug mexiletine. These findings provide an excellent illustration of a causal relationship between the interaction of the environment and genetic background in SIDS and also raise interesting questions about the linkage of a genetic abnormality with a clinical phenotype.
在本期《临床研究杂志》中，鲍尔斯等人指出，在非裔美国人中发现的心脏电压门控钠通道α型（SCN5A）的常见多态性，即S1103Y，与婴儿猝死综合征（SIDS）风险增加有关。野生型和突变型SCN5A通道在体外正常条件下功能均正常，但暴露于酸性细胞内pH水平，如呼吸性酸中毒（已知的SIDS风险因素）时，S1103Y通道会出现异常的功能获得性晚期再开放，这种行为通常与心律失常有关。这些病理性晚期再开放可被低水平的通道阻断药物美西律抑制。这些发现很好地说明了SIDS中环境与遗传背景相互作用之间的因果关系，也提出了关于基因异常与临床表型关联的有趣问题。
