Home Medizin Die schützende Wirkung von Koffein gegen Fettleibigkeit und Gelenkerkrankungen wird durch genetische Studien bestätigt

Die schützende Wirkung von Koffein gegen Fettleibigkeit und Gelenkerkrankungen wird durch genetische Studien bestätigt

von NFI Redaktion

A recent study published in BMC Medicine examined the effects of caffeine levels in circulation by considering genetically predicted variations in caffeine metabolism.

Study: Genetic investigation of the far-reaching health effects of caffeine: Evidence from phenotype-wide, proteome-wide, and metabolome-wide Mendelian randomization. Image Source: portumen/Shutterstock.comStudy: Genetic investigation of the far-reaching health effects of caffeine: Evidence from phenotype-wide, proteome-wide, and metabolome-wide Mendelian randomization. Image Source: portumen/Shutterstock.com

Background

Caffeine, a bioactive molecule of plant origin, is a popular psychoactive stimulant with therapeutic effects that are unclear due to its interaction with consumption habits and metabolism.

It penetrates cell membranes and acts as an antagonist to adenosine receptors in the brain, adipose tissue, cardiovascular, renal, gastrointestinal, and respiratory systems, exerting a rapid effect in all organ systems.

Previous studies used genetic variations to determine the causal influence of increased serum caffeine levels on the risk of type 2 diabetes and obesity; however, epidemiological and genetic studies on the health effects of coffee consumption yielded conflicting results.

About the Study

In this study, researchers analyzed data from a phenotype-wide association study (PheWAS) to evaluate the clinical effects of serum caffeine based on genetic variants related to caffeine metabolism affecting circulating levels.

The team derived a genetic risk score (GRS) for serum caffeine using single-nucleotide polymorphisms (SNPs) within the CYP1A2 and AHR genes strongly associated with serum caffeine levels.

They performed logistic regressions for each phenotypic code using standardized genetic risk scores for serum caffeine, adjusting for gender, age, and the first ten principal genetic components.

The PheWAS study included 988 clinical features recorded in participants of the United Kingdom Biobank (UKBB) to assess health outcomes associated with serum caffeine levels.

They conducted a metabolome- and proteome-wide Mendelian randomization analysis to elucidate the mechanisms responsible for the biological effects of serum caffeine on osteoarthritis, postmenopausal bleeding, as well as serum metabolites and proteins.

The team obtained genetic data for serum caffeine from a previous meta-analysis of genome-wide association studies (GWAS) involving 9,876 participants, predominantly Europeans aged 47 to 71 years.

They obtained genetic association data for osteoarthritis from a meta-analysis of 177,517 osteoarthritis cases at any site and 649,173 controls in 21 cohorts. The team identified postmenopausal bleeding cases based on International Classification of Diseases, Tenth Revision (ICD-10) codes.

To investigate potential pleiotropic effects that could lead to biases, the researchers stratified participants of the United Kingdom Biobank (UKBB) by the type of beverage consumed.

They used random-effects inverse variance weighted method to conduct bidirectional Mendelian randomization and determine the relationship between caffeine metabolism and caffeine intake.

The team assessed caffeine consumption based on self-reported coffee intake, obtaining genetic association information from 428,860 UKBB participants.

To evaluate the influence of body mass index (BMI) on the effects of serum caffeine on outcomes, they conducted a mediation analysis by multiplying MR estimates for the effects of serum caffeine on BMI by those for BMI effects on the study outcome.

Results

Higher genetically estimated caffeine levels in caffeine beverage drinkers were associated with reduced obesity (odds ratio, 0.97) and osteoarthritis (odds ratio, 0.97) risks. Lower body weight accounted for 33% of the protective effects of serum caffeine against osteoarthritis.

Metabolomic and proteomic analyses revealed improved lipid profiles, decreased chronic inflammation, and changes in glycogen and protein metabolism as biological pathways linked to caffeine effects.

In the PheWAS analysis, higher estimated circulating caffeine levels from the genetic risk score significantly lowered the risk of obesity and osteoarthritis outcomes. The weighted GRS for serum caffeine also correlated with increased postmenopausal bleeding risk.

Two-sample Mendelian randomization analyses showed a 10% reduction in the risk of osteoarthritis per standard deviation increase in caffeine. The team found no evidence of Mendelian randomization in two sample FinnGen consortium participants linking serum caffeine levels to postmenopausal bleeding risk (odds ratio, 1.2).

In the stratified analysis, a significant association was observed between genetically estimated serum caffeine levels and arthritis risk in coffee consumers, but not in non-drinkers.

The team also found a statistically significant association between BMI and genetically estimated serum caffeine levels in coffee or tea consumers, but not in abstainers.

Bidirectional Mendelian randomization examining the relationship between plasma caffeine and coffee consumption suggested a link between higher genetically estimated serum caffeine and lower coffee consumption, but not between genetically estimated coffee consumption and serum caffeine levels.

Conclusion

Overall, the study results provided evidence from proteome-wide, phenome-wide, and metabolome-wide MR analyses for the protective effects of caffeine against osteoarthritis and obesity risks, which is crucial given the global burden of obesity and osteoarthritis.

The study also found that higher plasma caffeine levels may reduce caffeine consumption. Future studies, including randomized clinical trials, may enhance understanding of the translational relevance of the study findings.

Related Posts

Adblock Detected

Please support us by disabling your AdBlocker extension from your browsers for our website.