多巴胺能去神经支配的严重程度取决于帕金森病中儿茶酚-O-甲基转移酶（COMT）基因Val158Met多态性。
Dopaminergic denervation severity depends on COMT Val158Met polymorphism in Parkinson's disease.
作者信息
Muellner Julia, Gharrad Iman, Habert Marie-Odile, Kas Aurélie, Martini Jean-Baptiste, Cormier-Dequaire Florence, Tahiri Khadija, Vidailhet Marie, Meier Niklaus, Brice Alexis, Schuepbach Michael, Mallet Alain, Hartmann Andreas, Corvol Jean-Christophe
机构信息
Department of Neurology, Inselspital, Freiburgstrasse 100, 3010 Bern, Switzerland; Sorbonne University, UPMC Paris 06 UMR S 1127, and Inserm U 1127 and CIC 1422, and CNRS UR 7225, and ICM, 75013 Paris, France.
Sorbonne University, UPMC Paris 06 UMR S 1127, and Inserm U 1127 and CIC 1422, and CNRS UR 7225, and ICM, 75013 Paris, France.
出版信息
Parkinsonism Relat Disord. 2015 May;21(5):471-6. doi: 10.1016/j.parkreldis.2015.02.009. Epub 2015 Feb 19.
BACKGROUND
Catecholamine-O-methyl-tranferase (COMT) initiates dopamine degradation. Its activity is mainly determined by a single nucleotide polymorphism in the COMT gene (Val158Met, rs4680) separating high (Val/Val, COMT(HH)), intermediate (Val/Met, COMT(HL)) and low metabolizers (Met/Met, COMT(LL)). We investigated dopaminergic denervation in the striatum in PD patients according to COMT rs4680 genotype.
METHODS
Patients with idiopathic PD were assessed for motor severity (UPDRS-III rating scale in OFF-state), dopaminergic denervation using [123I]-FP-CIT SPECT imaging, and genotyped for the COMT rs4680 enzyme. [123I]-FP-CIT binding potential (BP) for each voxel was defined by the ratio of tracer-binding in the region of interest (striatum, caudate nucleus and putamen) to that in a region of non-specific activity. Genotyping was performed using TaqMan(®) SNP genotyping assay. We used a regression model to evaluate the effect of COMT genotype on the BP in the striatum and its sub-regions.
RESULTS
Genotype distribution was: 11 (27.5%) COMT(HH), 26 (65%) COMT(HL) and 3 (7.5%) COMT(LL). There were no significant differences in disease severity, treatments, or motor scores between genotypes. When adjusted to clinical severity, gender and age, low and intermediate metabolizers showed significantly higher rates of striatal denervation (COMT(HL+LL) BP = 1.32 ± 0.04) than high metabolizers (COMT(HH), BP = 1.6 ± 0.08; F(1.34) = 9.0, p = 0.005). Striatal sub-regions showed similar results. BP and UPDRS-III motor scores (r = 0.44, p = 0.04) (p < 0.001) were highly correlated. There was a gender effect, but no gender-genotype interaction.
CONCLUSIONS
Striatal denervation differs according to COMT-Val158Met polymorphism. COMT activity may play a role as a compensatory mechanism in PD motor symptoms.
背景
儿茶酚-O-甲基转移酶（COMT）启动多巴胺降解。其活性主要由COMT基因中的一个单核苷酸多态性（Val158Met，rs4680）决定，该多态性将高代谢者（Val/Val，COMT(HH)）、中等代谢者（Val/Met，COMT(HL)）和低代谢者（Met/Met，COMT(LL)）区分开来。我们根据COMT rs4680基因型研究了帕金森病（PD）患者纹状体中的多巴胺能去神经支配情况。
方法
对特发性PD患者进行运动严重程度评估（关期统一帕金森病评定量表第三部分评分），使用[123I]-FP-CIT单光子发射计算机断层扫描（SPECT）成像评估多巴胺能去神经支配情况，并对COMT rs4680酶进行基因分型。每个体素的[123I]-FP-CIT结合潜能（BP）通过感兴趣区域（纹状体、尾状核和壳核）的示踪剂结合与非特异性活性区域的示踪剂结合之比来定义。基因分型使用TaqMan(®)单核苷酸多态性基因分型检测法。我们使用回归模型评估COMT基因型对纹状体及其亚区域BP的影响。
结果
基因型分布为：11例（27.5%）COMT(HH)、26例（65%）COMT(HL)和3例（7.5%）COMT(LL)。不同基因型在疾病严重程度、治疗方法或运动评分方面无显著差异。在根据临床严重程度、性别和年龄进行调整后，低代谢者和中等代谢者的纹状体去神经支配率（COMT(HL + LL)，BP = 1.32 ± 0.04）显著高于高代谢者（COMT(HH)，BP = 1.6 ± 0.08；F(1.34) = 9.0，p = 0.005）。纹状体亚区域显示出类似结果。BP与统一帕金森病评定量表第三部分运动评分（r = 0.44，p = 0.04）（p < 0.001）高度相关。存在性别效应，但不存在性别-基因型相互作用。
结论
纹状体去神经支配情况因COMT-Val158Met多态性而异。COMT活性可能在PD运动症状中作为一种代偿机制发挥作用。
Zotero 插件