Department of Neurology and Epileptology, Centre of Postgraduate Medical Education, Orłowski Hospital, Warsaw, Poland.
Department of Physical Education and Health in Biała Podlaska, Józef Piłsudski University of Physical Education in Warsaw, Biała Podlaska, Poland.
Brain Behav. 2020 Mar;10(3):e01537. doi: 10.1002/brb3.1537. Epub 2020 Feb 5.
The aim of the study was to evaluate the association of individual and combined single-nucleotide polymorphisms in brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and catechol-O-methyltransferase (COMT) genes with the occurrence of motor levodopa-induced complications (MLIC) in Parkinson's disease (PD).
We studied 76 patients with PD (MLIC occurred in 56.6%) and 60 controls. Allelic discrimination of rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) genes were genotyped. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using multinominal logistic regression. Orthogonal partial least squares (OPLS) analysis and OPLS discriminant analysis (OPLS-DA) were used to analyze qualitative genetic data.
The risk of PD in subjects with the AG BDNF genotype was increased sixfold (OR = 6.12, 95% CI = 2.88-13.02, p < .0001), and AG BDNF and AG DAT genotypes were correlated with PD in OPLS-DA (VIP > 1). There were no differences in distributions of BDNF, DAT and COMT genotypes between PD groups with and without MLIC, while OPLS model showed that genotype combination of AG BDNF, AG DAT, and GG COMT was correlated with MLIC and genotypes combination of GG BDNF, AA DAT, and AA COMT with lack of MLIC in PD patients (VIP > 1).
Our results confirmed the association of rs6265 BDNF (Val66Met) with the risk of PD and suggest a synergic effect of rs6265 BDNF (Val66Met), rs397595 DAT (SLC6A3), and rs4680 COMT (Val158Met) polymorphisms on the occurrence of MLIC.
本研究旨在评估脑源性神经营养因子（BDNF）、多巴胺转运体（DAT）和儿茶酚-O-甲基转移酶（COMT）基因的单个和联合单核苷酸多态性与帕金森病（PD）患者运动性左旋多巴诱导并发症（MLIC）发生的相关性。
我们研究了 76 例 PD 患者（MLIC 发生率为 56.6%）和 60 例对照者。对 rs6265BDNF（Val66Met）、rs397595DAT（SLC6A3）和 rs4680COMT（Val158Met）基因的等位基因进行了鉴别。使用多项逻辑回归计算比值比（OR）和 95%置信区间（95%CI）。采用正交偏最小二乘法（OPLS）分析和 OPLS 判别分析（OPLS-DA）分析定性遗传数据。
携带 BDNF 基因型 AG 的 PD 患者的发病风险增加了 6 倍（OR=6.12，95%CI=2.88-13.02，p<0.0001），AGBDNF 和 AGDAT 基因型在 OPLS-DA 中与 PD 相关（VIP>1）。在伴有和不伴有 MLIC 的 PD 患者组中，BDNF、DAT 和 COMT 基因型的分布无差异，而 OPLS 模型显示，AGBDNF、AGDAT 和 GGCONT 基因型组合与 MLIC 相关，GGBDNF、AADAT 和 AA COMT 基因型组合与 PD 患者缺乏 MLIC 相关（VIP>1）。
本研究结果证实了 rs6265BDNF（Val66Met）与 PD 风险的相关性，并提示 rs6265BDNF（Val66Met）、rs397595DAT（SLC6A3）和 rs4680COMT（Val158Met）多态性的协同作用可能与 MLIC 的发生有关。
