Department of Neurology, Beijing Huairou Hospital of Traditional Chinese Medicine, Beijing, China.
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Front Immunol. 2024 Aug 6;15:1412157. doi: 10.3389/fimmu.2024.1412157. eCollection 2024.
Increasing evidence suggests an association between (HP) infection and Parkinson's disease (PD) and its clinical manifestations, but the causal relationship remain largely unknown.
To investigate the causal relationship between HP infection and PD risk, PD symptoms, and secondary parkinsonism, we conducted two-sample Mendelian randomization (MR).
We obtained summary data from genome-wide association studies for seven different antibodies specific to HP proteins and five PD-related phenotypes. The inverse-variance weighted (IVW), weighted median, weighted mode, and MR-Egger methods were used to assess the causal relationships. Sensitivity analyses were performed to examine the stability of the MR results and reverse MR analysis was conducted to evaluate the presence of reverse causality.
Genetically predicted HP antibodies were not causally associated with an increased risk of PD. However, HP cytotoxin-associated gene-A (CagA) and outer membrane protein (OMP) antibody level were causally associated with PD motor subtype (tremor to postural instability/gait difficulty score ratio; = -0.16 and 0.46, = 0.002 and 0.048, respectively). HP vacuolating cytotoxin-A (VacA) antibody level was causally associated with an increased risk of PD dementia [odds ratio (OR) = 1.93, = 0.040]. Additionally, HP OMP antibody level was identified as a risk factor for drug-induced secondary parkinsonism (OR = 2.08, = 0.033). These results were stable, showed no evidence of heterogeneity or directional pleiotropy, and no evidence of a reverse causal relationship.
Our findings indicate that HP infection does not increase the risk of PD, but contributes to PD motor and cognitive symptoms. Different types of HP antibodies affect different symptoms of PD. Eradication of HP infection may help modulate and improve symptoms in PD patients.
越来越多的证据表明，幽门螺杆菌（HP）感染与帕金森病（PD）及其临床表现之间存在关联，但因果关系仍知之甚少。
为了探讨 HP 感染与 PD 风险、PD 症状和继发性帕金森病之间的因果关系，我们进行了两样本孟德尔随机化（MR）分析。
我们从针对七种不同 HP 蛋白抗体和五种 PD 相关表型的全基因组关联研究中获得了汇总数据。采用逆方差加权（IVW）、加权中位数、加权模式和 MR-Egger 方法来评估因果关系。进行敏感性分析以检查 MR 结果的稳定性，并进行反向 MR 分析以评估是否存在反向因果关系。
遗传预测的 HP 抗体与 PD 风险的增加没有因果关系。然而，HP 细胞毒素相关基因 A（CagA）和外膜蛋白（OMP）抗体水平与 PD 运动亚型（震颤至姿势不稳/步态困难评分比）呈因果关系（ = -0.16 和 0.46， = 0.002 和 0.048）。HP 空泡细胞毒素 A（VacA）抗体水平与 PD 痴呆的风险增加呈因果关系（比值比 [OR] = 1.93， = 0.040）。此外，HP OMP 抗体水平被确定为药物诱导的继发性帕金森病的危险因素（OR = 2.08， = 0.033）。这些结果是稳定的，没有异质性或方向性偏倚的证据，也没有反向因果关系的证据。
我们的研究结果表明，HP 感染不会增加 PD 的风险，但会导致 PD 的运动和认知症状。不同类型的 HP 抗体影响 PD 的不同症状。根除 HP 感染可能有助于调节和改善 PD 患者的症状。
