The association of functional catechol-O-methyltransferase haplotypes with risk of Parkinson's disease, levodopa treatment response, and complications
The association of functional catechol-O-methyltransferase haplotypes with risk of Parkinson's disease, levodopa treatment response, and complications
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DOI：
10.1097/fpc.0b013e328306c2f2
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发表时间：
2008-09-01
影响因子：
2.6
通讯作者：
Drozdzik, Marek
中科院分区：
文献类型：
--
作者：
Bialecka, Monika;Kurzawski, Mateusz;Drozdzik, Marek
儿茶酚-O-甲基转移酶（COMT）活性和基因型的差异可能决定对左旋多巴或帕金森病（PD）易感性的治疗反应的个体差异。功能性COMT单倍型在PD易感性和治疗反应中的作用还没有被研究。目的在这项病例对照研究中，我们调查了最常见的COMT基因单倍型与PD易感性和治疗反应的关系。（由单核苷酸多态性（SNP）形成：rs6269：A > G; rs 4633：C> T; rs 4818：C > G;和rs 4680：A > G）与PD风险的关系以及COMT单倍型与PD患者左旋多巴治疗剂量和并发症的关系。参与者（322名PD和357名对照）。每个参与者的COMT基因，位于一个共同的haploblock，已被证明会影响COMT酶活性的四个SNP的基因分型。在PD患者中检查COMT单倍型对治疗第五年期间给予的左旋多巴剂量和运动并发症发生率的影响。结果PD患者的低活性（A_C_C_G）和中活性（A_T_C_A）单倍型频率略低于对照组（P=0.09，以G-C-G-高活性单倍型为参考）。晚发性PD患者中G_C_G_G（高活性）单倍型携带者的频率高于对照组（P=0.04）。平均左旋多巴剂量随着功能单倍型的活性而增加（低<中<高）。G-C-G-G（高活性）单倍型携带者的处方剂量（平均604.2 ± 261.9 mg）显著高于非携带者（平均512.2 ± 133.5 mg，P
Introduction Differences in catechol-O-methyltransferase (COMT) activity and genotype may determine individual variations in the therapeutic response to levodopa or Parkinson's disease (PD) susceptibility. The role of functional COMT haplotypes in PD susceptibility and treatment response has not been examined.Objectives In this case-control study, we investigated the association of the most common COMT gene haplotypes (formed by single nucleoticle polymorphisms (SNPs): rs6269:A > G; rs4633C > T; rs4818:C > G; and rs4680:A > G) with PD risk and the association of the COMT haplotypes with the dose and complications of levodopa therapy in PD patients.Methods A total of 679 study participants (322 PD and 357 controls) were included. Each participant was genotyped for four SNPs in the COMT gene, located in a common haploblock, that has been shown to influence COMT enzymatic activity. The influence of COMT haplotypes on the dose of levodopa administered during fifth year of treatment and occurrence of motor complications were examined in PD patients. The EH program (Jurg Oft, Rockefeller University, New York, USA) was used to estimate haplotype frequencies.Results The estimated frequencies of low (A_C_C_G) and medium (AT C A) activity haplotypes tended to be slightly lower among PD patients when compared with controls (P=0.09, G-C-G-G-high activity haplotype as reference). The frequency of G_C_G_G (high activity) haplotype carriers was higher in late onset PD patients (P=0.04) compared with controls. The mean levodopa dose increased with the activity of the functional haplotypes (low < medium < high). Doses prescribed for G-C-G-G (high activity) haplotype carriers (mean 604.2 +/- 261.9 mg) were significantly higher than those for the noncarriers (mean 512.2 +/- 133.5 mg, P