by In a recent study published in Lancet Regional Health – Western Pacific, a group of researchers investigated the interaction of caffeine with Leucine rich repeat kinase 2 (LRRK2) genetic risk variants in Asians and evaluated the risk of Parkinson’s disease (PD) in caffeine drinkers carrying these variants.
Lesson: Caffeine intake interacts with Asian genetic variants in Parkinson’s disease: a study of 4488 subjects.. Image Credit: Danijela Maksimovic/Shutterstock.com
Background
PD is a common neurodegenerative condition characterized by tremors, slow movement, and coordination issues. Its incidence, especially in those over 65, increases the burden on society due to the aging of the population. The origins of PD are multifaceted, with both genetic and environmental influences.
Genes such as Alpha-synuclein, LRRK2, and Parkin play an important role in the progression of PD. LRRK2 mutations, particularly specific variants, are common risk factors in Asians.
Interestingly, studies have shown that caffeine can provide protective effects against PD, reducing the risk by 25% through its effect on the adenosine A2A receptor. Although genetics and environmental factors are studied independently in the context of PD, research on their role, especially the interaction of caffeine with PD-related genes, remains sparse.
About the study
The present study identified PD cases from two major movement disorder centers in Singapore, diagnosed based on the United Kingdom PD Society Brain Bank criteria. Healthy participants from the Community Health Evaluation Program served as controls. Consent was obtained, and the study conformed to SingHealth Centralized Institutional Review Board (CIRB) guidelines.
Using a validated questionnaire, participants provided demographics, family history, and caffeine use data through a clinical interview. The source of caffeine was coffee and tea.
Those who do not use caffeine have been identified as those who have zero lifestyle. For genetic analysis, blood samples were subjected to deoxyribonucleic acid (DNA) extraction and genotyping, and sequence verification.
The analysis took into account demographic factors such as age, sex, family history, and caffeine use. Various statistical tests assessed differences and genotype distributions, including Student’s t test and Fisher’s exact test.
Odds ratios (OR) evaluated each SNP association, determining the genetic model and the SNP-caffeine interaction. Participants were classified based on genetic risk and caffeine consumption. Adjusted OR calculated for age, sex, and family history.
The appropriateness of logistic regression was verified using the Hosmer–Lemeshow test. R version 3.4.2 and STATA version 14.0 supported the statistical analysis.
SNPassoc assisted in evaluating associations and selecting the best genetic model based on p-values.
Results of the study
In the present study, of the 5,100 subjects examined, 4,488 participants (88%) were included, with 1,790 PD cases and 2,698 controls. Exclusions were due to incomplete demographic/exposure information (4.5%) or genetic data (7.5%).
Among PD cases, 8.9% had a family history of movement disorders, and 11.2% were caffeine drinkers. The average age of PD was 62.3 years, while the control group had an average age of 52.5 years.
A significant positive association with PD was observed for the G2385R and R1628P variants, while the S1647T variant showed a non-significant negative association.
In assessing caffeine consumption, heterozygous carrier status for G2385R and R1628P was significantly associated with PD among caffeine drinkers. Non-caffeine drinkers who are homozygous S1647T carriers showed a stronger association with PD than caffeine drinkers.
When stratified by genotype, caffeine consumption was associated with a decreased likelihood of PD across all risk factors. Among the G2385R mutation carriers, the protective effect of caffeine was more pronounced in the mutation carriers.
G2385R mutation carriers who never consumed caffeine were eight times more likely to develop PD compared to wild-type caffeine drinkers. The combined risk exposure group had more problems than the single risk groups.
A positive biological interaction was characterized by values relative to the excess risk due to interaction (RERI), index of synergy (S), and proportionality ratio (AP) due to interaction.
A similar relationship was seen for the R1628P and S1647T variants, where those with a high genetic risk who never consumed caffeine had a fourfold increased risk of PD compared to those with a low genetic risk who drank caffeine.
Interestingly, among all risk factors, caffeine drinkers had a lower chance of developing PD than genetic low-risk non-caffeine drinkers. This suggests that the protective effect of caffeine may be offset by a differentially expressed genetic risk.
Analysis of caffeine intake revealed an average consumption of 448.3 mg-decade in PD cases and 473.0 mg-decade in controls. Due to the variability of responses, the accuracy of these estimates was limited.
The study further divided caffeine doses into low, moderate, and high. Among carriers of various risk factors, a trend was observed linking higher caffeine intake to lower odds of PD. Still, it was not statistically significant, possibly due to differences in dose estimates.
Conclusions
The present study examined the significant interaction between caffeine and three LRRK2 risk factors associated with PD.
Non-caffeine carriers of these risk factors are four to eight times more likely to develop PD than those without risk factors.
While the exact mechanisms behind this interaction remain unknown, they suggest caffeine’s potential neuroprotective role, by affecting the LRRK2 protein.
These findings provide a promising avenue for personalized prevention interventions, highlighting the potential benefits of caffeine consumption for those at high genetic risk.
However, the results are particularly important for the Asian population studied, and further research in different populations is needed.
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