Genetic analysis of the rhabdomyolysis-associated genes in forensic autopsy cases of methamphetamine abusers
Genetic analysis of the rhabdomyolysis-associated genes in forensic autopsy cases of methamphetamine abusers
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DOI：
10.1016/j.legalmed.2010.08.007
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发表时间：
2011-01-01
期刊：
影响因子：
1.5
通讯作者：
Kubo, Shin-ichi
中科院分区：
文献类型：
--
作者：
Matsusue, Aya;Hara, Kenji;Kubo, Shin-ichi
甲基苯丙胺（MA）的使用有时会导致横纹肌溶解，这与死亡率有关。我们分析了潜在的横纹肌溶解症的易感基因从尸检样本的18甲基苯丙胺滥用者。我们检测了兰尼碱受体1（RYR 1）、肉毒碱棕榈酰转移酶II（CPT II）、极长链酰基辅酶A脱氢酶（VLCAD）和细胞色素P450（CYP2D6）基因的突变。在2例患者中发现了不同的RYR1突变，导致氨基酸替换（（612）Ala > Thr和（4295）Ala >瓦尔）。CPT Ⅱ基因突变1例（545）Glu > Ala，突变不改变活性17例。在VLCAD基因中，有6例突变没有改变活性。在CYP2D6基因中，在3例病例中发现与代谢活性显著降低相关的CYP2D6*10纯合性，而2例病例携带不同的先前未报告的错义突变（（344）Arg > Gln和（48）His > Tyr）。在对照组中未观察到RYR1突变和本研究中鉴定的新CPT II突变。对18例进行了遗传学分析的病例进行了免疫组化检查，以诊断横纹肌溶解症的可能性。然而，在疑似横纹肌溶解病例中，没有出现导致酶活性降低的显着突变。这些数据表明，在本研究中观察到的基因突变与横纹肌溶解症之间没有明显的关系。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Methamphetamine (MA) use sometimes causes rhabdomyolysis, which has been associated with mortality. We analyzed potential rhabdomyolysis-susceptibility genes from autopsy samples of 18 methamphetamine abusers. We examined mutations in the ryanodine receptor 1 (RYR 1), carnitine palmitoyl-transferase II (CPT II), very long-chain acyl-CoA dehydrogenase (VLCAD), and cytochrome P450 (CYP) 2D6 genes. Different RYR1 mutations that caused amino acid substitutions ((612)Ala > Thr and (4295)Ala > Val) were identified in 2 cases. In the CPT II gene, there was a new mutation ((545)Glu > Ala) in 1 case and there were mutations that did not change activity in 17 cases. In the VLCAD gene, there were mutations that did not change activity in 6 cases. In the CYP2D6 gene, homozygosity for CYP2D6*10, which is associated with significantly reduced metabolic activity, was found in 3 cases, while 2 cases carried a different previously unreported missense mutation ((344)Arg > Gln and (48)His > Tyr). RYR1 mutations and the new CPT II mutation identified in this study were not observed in a control group. Eighteen cases that were genetically analyzed were also investigated immunohistochemically to diagnose the possibility of rhabdomyolysis. However, there were no significant mutations that reduced enzyme activity in the suspected cases of rhabdomyolysis. These data suggested no obvious relationship between the genetic mutations observed in this study and rhabdomyolysis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.