Dataset Information

Nutrition and Rheumatoid Arthritis in the 'Omics' Era.

ABSTRACT: Modern high-throughput 'omics' science tools (including genomics, transcriptomics, proteomics, metabolomics and microbiomics) are currently being applied to nutritional sciences to unravel the fundamental processes of health effects ascribed to particular nutrients in humans and to contribute to more precise nutritional advice. Diet and food components are key environmental factors that interact with the genome, transcriptome, proteome, metabolome and the microbiota, and this life-long interplay defines health and diseases state of the individual. Rheumatoid arthritis (RA) is a chronic autoimmune disease featured by a systemic immune-inflammatory response, in genetically susceptible individuals exposed to environmental triggers, including diet. In recent years increasing evidences suggested that nutritional factors and gut microbiome have a central role in RA risk and progression. The aim of this review is to summarize the main and most recent applications of 'omics' technologies in human nutrition and in RA research, examining the possible influences of some nutrients and nutritional patterns on RA pathogenesis, following a nutrigenomics approach. The opportunities and challenges of novel 'omics technologies' in the exploration of new avenues in RA and nutritional research to prevent and manage RA will be also discussed.

SUBMITTER: Cassotta M

PROVIDER: S-EPMC7996781 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Nutrition and Rheumatoid Arthritis in the 'Omics' Era.

Cassotta Manuela M Forbes-Hernandez Tamara Y TY Cianciosi Danila D Elexpuru Zabaleta Maria M Sumalla Cano Sandra S Dominguez Irma I Bullon Beatriz B Regolo Lucia L Alvarez-Suarez Josè Miguel JM Giampieri Francesca F Battino Maurizio M

Nutrients 20210226 3

Modern high-throughput 'omics' science tools (including genomics, transcriptomics, proteomics, metabolomics and microbiomics) are currently being applied to nutritional sciences to unravel the fundamental processes of health effects ascribed to particular nutrients in humans and to contribute to more precise nutritional advice. Diet and food components are key environmental factors that interact with the genome, transcriptome, proteome, metabolome and the microbiota, and this life-long interplay ...[more]

PMID: 33652915

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Project description:BackgroundAutophagy is associated with the development of rheumatoid arthritis (RA), but its genetic pathological mechanisms remain incompletely understood. In this study, we employed summary-data-based Mendelian randomization (SMR) and co-localization analysis to systematically investigate the relationship between autophagy-related genes and RA.MethodsWe obtained summary data on blood methylation (mQTL), gene expression (eQTL), and protein abundance (pQTL) from respective quantitative trait locus (QTL) studies. Genetic association data for RA were primarily derived from the FinnGen database, with validation performed using the UK Biobank (UKB) and GWAS Catalog databases. SMR analysis was conducted to evaluate the association between molecular characteristics of autophagy-related genes and RA. Subsequently, co-localization analysis was performed to determine whether the identified signals share the same causal genetic variants.ResultsAfter integrating mQTL-eQTL multi-omics data, we identified two key autophagy genes, BCL2L1 and RAF1, which may have a causal relationship with RA. Significant associations were found for BCL2L1 (cg12873919, cg13989999) and RAF1 (cg26432171) in the SMR analysis of autophagy-related mQTL, eQTL, and GWAS data (p SMR < 0.05). In the integrated mQTL-eQTL SMR analysis, cg12873919 (p SMR = 1.40E-07, OR = 0.82, 95% CI [0.76-0.88]), cg13989999 (p SMR = 1.43E-06, OR = 0.78, 95% CI [0.71-0.87]), and cg26432171 (p SMR = 9.18E-09, OR = 1.83, 95% CI [1.49-2.25]) were all significantly validated. Methylation of cg12873919 and cg13989999 in BCL2L1 was associated with increased BCL2L1 expression, consistent with their negative impact on RA risk. Conversely, the cg26432171 site in RAF1 showed a positive correlation between gene methylation and expression. In the eQTL-GWAS SMR analysis, MAPK3 expression (p SMR = 7.24E-05, OR = 0.91, 95% CI [0.87-0.95]) was negatively correlated with RA risk, a finding supported by co-localization analysis (PPH4 > 0.5), suggesting that this gene may inhibit RA pathogenesis by regulating the autophagy process. Furthermore, protein level analysis also supported the protective role of MAPK3 (p SMR = 7.53E-05, OR = 0.89, 95% CI [0.84-0.94]).ConclusionWe identified that autophagy-related genes BCL2L1 and RAF1 may be associated with RA risk, providing strong evidence from multi-omics data. This study identifies autophagy genes related to RA, potentially offering new insights into the pathogenesis of RA.

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Nutrition and Rheumatoid Arthritis in the 'Omics' Era.

Publications

Nutrition and Rheumatoid Arthritis in the 'Omics' Era.

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