背景:咖啡因是全球消费最多的精神活性物质之一。咖啡因基因在帕金森病(PD)中的相互作用尚未被系统研究。
目的:对咖啡因摄入与PD遗传易感性之间的相互作用进行系统评价。
方法:我们使用术语“遗传关联研究”进行PubMed和Embase搜索,\"咖啡因\",“多态性”和“帕金森病”,从成立到2023年。在最初的2391项研究中,纳入21项病例对照研究。人口统计,遗传和临床资料进行提取和分析。
结果:我们确定了21项研究,涉及总共607,074名研究对象和17个基因位点(SNCA,MAPT,HLA-DRA,NOS1,NOS3,GBA,ApoE,BST1,ESR2,NAT2,SLC2A13,LRRK2,NOS2A,GRIN2A,CYP1A2,ESR1,ADORA2A)已经研究了基因-咖啡因相互作用和PD风险的影响。这些基因是通过PDGWAS鉴定的,或者参与咖啡因或相关的代谢途径。基于遗传关联和相互作用研究,只有MAPT,SLC2A13,LRRK2,ApoE,NOS2A,GRIN2A,至少一项研究表明,CYP1A2和ADORA2A具有积极的咖啡因-基因相互作用,影响PD的风险。
结论:研究表明咖啡因与MAPT的遗传变异体之间存在相互作用,SLC2A13,LRRK2,ApoE,NOS2A,GRIN2A,CYP1A2和ADORA2A在调节PD风险中的作用。由于这些发现/试点研究的潜在局限性,需要进一步的独立复制研究.在多血统和混合队列中设计更好的遗传关联研究,以识别潜在的共享或独特的多变量基因-环境相互作用,以及基因-咖啡因相互作用的功能研究将是有用的。
BACKGROUND: Caffeine is one of the most consumed psychoactive substances globally.
Caffeine-gene interactions in Parkinson\'s disease (PD) has not been systematically examined.
OBJECTIVE: To conduct a systematic
review on the interaction between
caffeine consumption and genetic susceptibility to PD.
METHODS: We conducted PubMed and Embase search using terms \"Genetic association studies\", \"
Caffeine\", \"polymorphism\" and \"Parkinson\'s disease\", from inception till 2023. Of the initial 2391 studies, 21 case-control studies were included. The demographic, genetic and clinical data were extracted and analyzed.
RESULTS: We identified 21 studies which involved a total of 607,074 study subjects and 17 gene loci (SNCA, MAPT, HLA-DRA, NOS1, NOS3, GBA, ApoE, BST1, ESR2, NAT2, SLC2A13, LRRK2, NOS2A, GRIN2A, CYP1A2, ESR1, ADORA2A) have been investigated for the effect of gene-caffeine interaction and PD risk. The genes were identified through PD GWAS or involved in
caffeine or related metabolism pathways. Based on the genetic association and interaction studies, only MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2, and ADORA2A have been shown by at least one study to have a positive caffeine-gene interaction influencing the risk of PD.
CONCLUSIONS: Studies have shown an interaction between caffeine with genetic variants of MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2, and ADORA2A in modulating the risk of PD. Due to the potential limitations of these discovery/pilot studies, further independent replication studies are needed. Better designed genetic association studies in multi-ancestry and admixed cohorts to identify potential shared or unique multivariate gene-environmental interactions, as well as functional studies of gene-caffeine interactions will be useful.