Interaction between caffeine consumption & genetic susceptibility in Parkinson's disease: A systematic review.

Caffeine is one of the most consumed psychoactive substances globally. Caffeine-gene interactions in Parkinson's disease (PD) has not been systematically examined. To conduct a systematic review on the interaction between caffeine consumption and genetic susceptibility to PD. 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. 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. 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. [Display omitted] • Caffeine is one of the most consumed psychoactive substances globally. • Caffeine is an antagonist of adenosine A2A receptor and caffeine consumption can be protective against PD. • Results from 21 studies involving 607,074 human subjects and 17 gene loci are investigated to understand the interplay of caffeine and genetic factors in PD risk. • Eight genes, including MAPT, SLC2A13, LRRK2, ApoE, NOS2A, GRIN2A, CYP1A2 , and ADORA2A , are identified to have a positive caffeine-gene interaction to influence PD risk. [ABSTRACT FROM AUTHOR]