3 research outputs found
Supplementary Material for: Proceedings of the 11th Congress of the International Society of Nutrigenetics and Nutrigenomics (ISNN 2017)
<p>The International Society of Nutrigenetics and Nutrigenomics (ISNN)
held its 11th annual Congress in Los Angeles, California, between
September 16 and 19, 2017. In addition to 2 keynote lectures, 4 plenary
sessions included presentations by internationally renowned speakers on
cutting-edge areas of research and new discoveries in genetics/genomics,
the microbiome, and nutrition. Scientific topics included multi-omics
approaches; diet and the microbiome; cancer, longevity, and metabolism;
moving the field forward; and translational/educational aspects and the
future of medicine. There was also an accepted oral abstracts session
designed specifically to provide young investigators and trainees with
the opportunity to present their work, as well as a session focused on
industry-academic partnerships, which included a roundtable discussion
afterwards. Overall, the 11th ISNN Congress was an exciting and
intellectually stimulating meeting focused on understanding the impact
of biological interactions between genes and nutrients on health and
disease. These efforts continued the decade-long tradition of the annual
ISNN Congress to provide an interdisciplinary platform for scientists
from various disciplines to discuss research ideas and advance the
fields of nutrigenetics and nutrigenomics.</p
Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality
Aims Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1 beta can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.Methods and results We explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.Conclusion The NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.[GRAPHICS].Pathophysiology, epidemiology and therapy of agein