Abstract
Gout is the most frequent form of inflammatory arthritis in the world. Its prevalence is particularly elevated in specific geographical areas such as in the Oceania/Pacific region and is rising in the US, Europe, and Asia. Gout is a severe and painful disease, in which co-morbidities are responsible for a significant reduction in life expectancy. However, gout patients remain ostracized because the disease is still considered “self-inflicted”, as a result of unhealthy lifestyle and excessive food and alcohol intake. While the etiology of gout flares is clearly associated with the presence of monosodium urate (MSU) crystal deposits, several major questions remain unanswered, such as the relationships between diet, hyperuricemia and gout flares or the mechanisms by which urate induces inflammation. Recent advances have identified gene variants associated with gout incidence. Nevertheless, genetic origins of gout combined to diet-related possible uric acid overproduction account for the symptoms in only a minor portion of patients. Hence, additional factors must be at play. Here, we review the impact of epigenetic mechanisms in which nutrients (such as ω-3 polyunsaturated fatty acids) and/or dietary-derived metabolites (like urate) trigger anti/pro-inflammatory responses that may participate in gout pathogenesis and severity. We propose that simple dietary regimens may be beneficial to complement therapeutic management or contribute to the prevention of flares in gout patients.
Highlights
Gout is probably the oldest known joint disease, already described by Hippocrates of Kos in the fifth century B.C [1]
This meta-analysis concerned patients of European ancestry and may not be generalized to other ethnic groups ( those, like Oceanians [4] in which gout represents a major public healthcare issue), it highlights the importance of genetic variants identified in genome-wide association studies (GWAS), which account for almost one fourth (23.9%) of the variation of serum urate levels compared to 0.3% associated with diet
Diets using longer poly-unsaturated fatty acids (PUFA), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have been shown to have beneficial effects on cancer cell lines and patients suffering of various types of cancer, through lowering inflammation [for review, see [77]], but perhaps most importantly in the context of this review, through a mechanism leading to a global hyperacetylation of histone N-termini, as well as at specific loci [94]
Summary
Gout is probably the oldest known joint disease, already described by Hippocrates of Kos in the fifth century B.C [1]. In line with these assumptions, it is noteworthy to highlight that genome-wide association studies (GWAS) comparing gout patients to control groups have identified variants in genes encoding important players in epigenetic regulation mechanisms, such as DNA Methyl Transferase 1 (DNMT1) [9] and lncRNAs [10].
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