1) that caffeine is causally associated with PD (i.e. something about caffeine truly reduces ones risk),
2) that the association is driven by reverse causation (i.e. in the pre-diagnostic phase of PD people have less of a tendency to consume caffeinated drinks and the effect of this reduction means that those that do consume caffeine appear relatively protected from PD), and
3) that the association is driven by a third factor (i.e. confounding - for example caffeine consumption is associated smoking and it is in fact smoking that is protective against PD).
The authors here try to go a step further and look at whether or not certain genetic variants explain some of the variation in PD risk with caffeine intake... their hypothesis was that the protective effect of caffeine may depend on whether you carry one gene variant or another... they did not observe any convincing evidence of this... but interaction tests such as these are notoriously underpowered (meaning that although it was a relatively big study, there may have been insufficient participants included to give the correct answer).
Overall the jury is still out on caffeine and risk of PD. One clinical trial a few years ago suggested that caffeine may reduce the motor symptoms of PD, but the follow up randomised trial failed to meet its primary end point, and perhaps most importantly, did not continue to the point that it tested whether caffeine might affect the underlying disease process.
- Alastair Noyce
Mov Disord. 2018 Jan 10. doi: 10.1002/mds.27279. [Epub ahead of print]
Kim IY, O'Reilly ÉJ, Hughes KC, Gao X, Schwarzschild MA, McCullough ML, Hannan MT, Betensky RA, Ascherio A.
http://onlinelibrary.wiley.com/wol1/doi/10.1002/mds.27279/abstract
BACKGROUND: Caffeine intake has been inversely associated with Parkinson's disease (PD) risk. This relationship may be modified by polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2), but the results of previous studies have been inconsistent.
METHOD: We examined the interaction of caffeine intake with GRIN2A-rs4998386 and CYP1A2-rs762551 polymorphisms in influencing PD risk among 829 incident cases of PD and 2,754 matched controls selected among participants in the following 3 large prospective ongoing cohorts: the Nurses' Health Study, the Health Professionals' Follow-up Study, and the Cancer Prevention Study II Nutrition Cohort. Matching factors included cohort, birth year, source of DNA, date of DNA collection, and race. Relative risks and 95% confidence intervals were estimated using conditional logistic models. Interactions were tested both on the multiplicative scale and on the additive scale.
RESULTS: Overall, caffeine intake was associated with a lower PD risk (adjusted relative risk for highest versus lowest tertile = 0.70; 95% confidence interval, 0.57-0.86; p < .001). In analyses stratified by the GRIN2A-rs4998386 genotype, the multivariable-adjusted relative risk of PD comparing the highest to the lowest tertile of caffeine was 0.69 (95% confidence interval, 0.55-0.88; p < .01) among individuals homozygous for the C allele, and 0.85 (95% confidence interval, 0.55-1.32; p = .47; pRERI = .43) among carriers for the T allele. Interactions between caffeine and GRIN2A were not significant in either the multiplicative or additive scales. We also did not observe significant interactions for CYP1A2-rs762551 and incident PD risk.
CONCLUSION: Our findings do not support the hypothesis of an interaction between the GRIN2A-rs4998386 or CYP1A2-rs762551 polymorphism and caffeine intake in determining PD risk.
© 2018 International Parkinson and Movement Disorder Society.
No comments:
Post a Comment