首页> 外文期刊>Journal of human genetics >Molecular analysis of potassium ion channel genes in sudden death cases among patients administered psychotropic drug therapy: Are polymorphisms in LQT genes a potential risk factor?
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Molecular analysis of potassium ion channel genes in sudden death cases among patients administered psychotropic drug therapy: Are polymorphisms in LQT genes a potential risk factor?

机译:接受精神药物治疗的患者中猝死病例钾离子通道基因的分子分析:LQT基因多态性是否是潜在的危险因素?

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Psychotropic drugs can pose the risk of acquired long QT syndrome (LQTS). Unexpected autopsy-negative sudden death in patients taking psychotropic drugs may be associated with prolonged QT intervals and life-threatening arrhythmias. We analyzed genes that encode for cardiac ion channels and potentially associated with LQTS, examining specifically the potassium channel genes KCNQ1 and KCNH2 in 10 cases of sudden death involving patients administered psychotropic medication in which autopsy findings identified no clear cause of death. We amplified and sequenced all exons of KCNQ1 and KCNH2, identifying G643S, missense polymorphism in KCNQ1, in 6 of the 10 cases. A study analysis indicated that only 11% of 381 healthy Japanese individuals carry this polymorphism. Reports of previous functional analyses indicate that the G643S polymorphism in the KCNQ1 potassium channel protein causes mild I Ks channel dysfunction. Our present study suggests that administering psychotropic drug therapy to individuals carrying the G643S polymorphism may heighten the risk of prolonged QT intervals and life-threatening arrhythmias. Thus, screening for the G643S polymorphism before prescribing psychotropic drugs may help reduce the risk of unexpected sudden death.
机译:精神药物可能会导致获得性长QT综合征(LQTS)。服用精神药物的患者意外尸检阴性猝死可能与延长QT间隔时间和危及生命的心律不齐有关。我们分析了编码心脏离子通道并可能与LQTS相关的基因,并特别检查了10例涉及精神药物患者的猝死病例中的钾通道基因KCNQ1和KCNH2,其中尸检结果没有明确的死亡原因。我们在10例病例中的6例中扩增并测序了KCNQ1和KCNH2的所有外显子,鉴定出G643S,即KCNQ1的错义多态性。一项研究分析表明,在381位健康的日本人中,只有11%携带这种多态性。先前功能分析的报告表明,KCNQ1钾通道蛋白中的G643S多态性会导致轻度的I Ks通道功能障碍。我们目前的研究表明,对携带G643S多态性的个体进行精神药物治疗可能会增加QT间隔延长和危及生命的心律失常的风险。因此,在开精神药物之前先筛查G643S多态性可能有助于降低意外猝死的风险。

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