No association between Parkinson's disease and low-activity alleles of catechol O-methyltransferase
No association between Parkinson's disease and low-activity alleles of catechol O-methyltransferase
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DOI：
10.1006/bbrc.1996.1731
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发表时间：
1996-11-21
影响因子：
3.1
通讯作者：
Collier, DA
中科院分区：
文献类型：
--
作者：
Hoda, F;Nicholl, D;Collier, DA
特发性帕金森病 (IPD) 的特征是黑质中色素神经元的丧失，导致酪氨酸羟化酶活性降低和多巴胺耗竭。治疗尝试通过使用左旋多巴和多巴胺代谢酶抑制剂（例如儿茶酚-O-甲基转移酶（COMT））来纠正这种缺陷。 COMT 中常见的氨基酸多态性（缬氨酸-108-甲硫氨酸）会导致酶的低活性形式，我们假设这可能会影响对 IPD 的易感性。我们使用 PCR-RFLP 和新型扩增阻滞突变系统 (ARMS) 测定法，在 139 名患有 IPD 的白人受试者和 173 名对照受试者中检查了这种多态性。受影响受试者和对照受试者的等位基因和基因型频率相似，表明 COMT 活性的变异不是 IPD 的病因因素。我们还鉴定了一种新的多态性 256C/G，它与 IPD 无关。然而，COMT 的等位基因变异仍然有可能影响严重程度、病理类型或对左旋多巴或 COMT 抑制剂的治疗反应。 (C) 1996 学术出版社
Idiopathic Parkinson's disease (IPD) is characterised by the loss of pigmented neurones in the substantia nigra leading to reduced tyrosine hydroxylase activity and depletion of dopamine. Treatments attempt to correct this deficit by the use of levodopa and inhibitors of dopamine metabolising enzymes such as catechol-O-methytransferase (COMT). A common amino-acid polymorphism in COMT, valine-108-methionine, results in a low activity form of the enzyme which we hypothesised may influence susceptibility to IPD. We examined this polymorphism in 139 Caucasian subjects viith IPD and 173 control subjects, using a PCR-RFLP and a novel Amplification Refractory Mutation System (ARMS) assay. Allele and genotype frequencies were similar in the affected and control subjects, indicating that variation of COMT activity is not an aetiological factor in IPD. We have also characterised a new polymorphism, 256C/G, which is not associated with IPD. However it remains possible that allelic variation in COMT influences severity, type of pathology or treatment response to levodopa or COMT inhibitors. (C) 1996 Academic Press, Inc.