Ma Xuning, Liao Zijun, Tan Henghui, Wang Kaitao, Feng Cuilian, Xing Pengpeng, Zhang Xiufen, Hua Junjie, Jiang Peixin, Peng Sibo, Lin Hualiang, Liang Wen, Gao Xiaoya
Department of Pediatric Neurology, Zhujiang Hospital of Southern Medical University, 253 Gongye Avenue, Guangzhou, Guangdong 510282, PR China.
Department of Neurology, Zhujiang Hospital of Southern Medical University, 253 Gongye Avenue, Guangzhou, Guangdong 510282, PR China.
EClinicalMedicine. 2024 Jul 25;74:102757. doi: 10.1016/j.eclinm.2024.102757. eCollection 2024 Aug.
Certain viral infections have been linked to the development of neurodegenerative diseases. This study aimed to investigate the association between cytomegalovirus (CMV) infection and five neurodegenerative diseases, spinal muscular atrophy (SMA) and related syndromes, Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and disorders of the autonomic nervous system (DANS).
This prospective cohort included white British individuals who underwent CMV testing in the UK Biobank from January 1, 2006 to December 31, 2021. A Cox proportional hazard model was utilized to estimate the future risk of developing five neurodegenerative diseases in individuals with or without CMV infection, adjusted for batch effect, age, sex, and Townsend deprivation index in Model 1, and additionally for type 2 diabetes, cancer, osteoporosis, vitamin D, monocyte count and leukocyte count in Model 2. Bidirectional Mendelian randomization was employed to validate the potential causal relationship between CMV infection and PD.
A total of 8346 individuals, consisting of 4620 females (55.4%) and 3726 males (44.6%) who were white British at an average age of 56.74 (8.11), were included in this study. The results showed that CMV infection did not affect the risk of developing AD (model 1: HR [95% CI] = 1.01 [0.57, 1.81], = 0.965; model 2: HR = 1.00 [0.56, 1.79], = 0.999), SMA and related syndromes (model 1: HR = 3.57 [0.64, 19.80], = 0.146; model 2: HR = 3.52 [0.63, 19.61], = 0.152), MS (model 1: HR = 1.16 [0.45, 2.97], = 0.756; model 2: HR = 1.16 [0.45, 2.97], = 0.761) and DANS (model 1: HR = 0.65 [0.16, 2.66], = 0.552; model 2: HR = 0.65 [0.16, 2.64], = 0.543). Interestingly, it was found that participants who were CMV seronegative had a higher risk of developing PD compared to those who were seropositive (model 1: HR = 2.37 [1.25, 4.51], = 0.009; model 2: HR = 2.39 [1.25, 4.54], = 0.008) after excluding deceased individuals. This association was notably stronger in males (model 1: HR = 3.16 [1.42, 7.07], = 0.005; model 2: HR = 3.41 [1.50, 7.71], = 0.003), but no significant difference was observed in the female subgroup (model 1: HR = 1.28 [0.40, 4.07], = 0.679; model 2: HR = 1.27 [0.40, 4.06], = 0.684). However, a bidirectional Mendelian randomization analysis did not find a genetic association between CMV infection and PD.
The study found that males who did not have a CMV infection were at a higher risk of developing PD. The findings provided a new viewpoint on the risk factors for PD and may potentially influence public health approaches for the disease.
National Natural Science Foundation of China (81873776), Natural Science Foundation of Guangdong Province, China (2021A1515011681, 2023A1515010495).
某些病毒感染与神经退行性疾病的发生有关。本研究旨在调查巨细胞病毒（CMV）感染与五种神经退行性疾病、脊髓性肌萎缩症（SMA）及相关综合征、帕金森病（PD）、阿尔茨海默病（AD）、多发性硬化症（MS）和自主神经系统疾病（DANS）之间的关联。
这项前瞻性队列研究纳入了2006年1月1日至2021年12月31日在英国生物银行接受CMV检测的英国白人个体。采用Cox比例风险模型估计CMV感染阳性或阴性个体发生五种神经退行性疾病的未来风险，模型1对批次效应、年龄、性别和汤森贫困指数进行了校正，模型2在此基础上还对2型糖尿病、癌症、骨质疏松症、维生素D、单核细胞计数和白细胞计数进行了校正。采用双向孟德尔随机化方法验证CMV感染与PD之间的潜在因果关系。
本研究共纳入8346名个体，其中4620名女性（55.4%）和3726名男性（44.6%），平均年龄56.74岁（8.11岁），均为英国白人。结果显示，CMV感染不影响发生AD的风险（模型1：HR[95%CI]=1.01[0.57,1.81]，P=0.965；模型2：HR=1.00[0.56,1.79]，P=0.999）、SMA及相关综合征（模型1：HR=3.57[0.64,19.80]，P=0.146；模型2：HR=3.52[0.63,19.61]，P=0.152）、MS（模型1：HR=1.16[0.45,2.97]，P=0.756；模型2：HR=1.16[0.45,2.97]，P=0.761）和DANS（模型1：HR=0.65[0.16,2.66]，P=0.552；模型2：HR=0.65[0.16,2.64]，P=0.543）。有趣的是，排除死亡个体后发现，CMV血清学阴性的参与者发生PD的风险高于血清学阳性者（模型1：HR=2.37[1.25,4.51]，P=0.009；模型2：HR=2.39[1.25,4.54]，P=0.008）。这种关联在男性中尤为明显（模型1：HR=3.16[1.42,7.07]，P=0.005；模型2：HR=3.41[1.50,7.71]，P=0.003），但在女性亚组中未观察到显著差异（模型第一：HR=1.28[0.40,4.07]，P=0.679；模型2：HR=1.27[0.40,4.06]，P=0.684）。然而，双向孟德尔随机化分析未发现CMV感染与PD之间存在遗传关联。
该研究发现未感染CMV的男性患PD的风险更高。这些发现为PD的风险因素提供了新的观点，并可能影响该疾病的公共卫生应对措施。
中国国家自然科学基金（81873776）、中国广东省自然科学基金（2021A1515011681、2023A1515010495）。
