Dataset Information

Large Scale Metabolic Profiling identifies Novel Steroids linked to Rheumatoid Arthritis.

ABSTRACT: Recent metabolomics studies of Rheumatoid Arthritis (RA) reported few metabolites that were associated with the disease, either due to small cohort sizes or limited coverage of metabolic pathways. Our objective is to identify metabolites associated with RA and its cofounders using a new untargeted metabolomics platform. Moreover, to investigate the pathomechanism of RA by identifying correlations between RA-associated metabolites. 132 RA patients and 104 controls were analyzed for 927 metabolites. Metabolites were tested for association with RA using linear regression. OPLS-DA was used to discriminate RA patients from controls. Gaussian Graphical Models (GGMs) were used to identify correlated metabolites. 32 metabolites are identified as significantly (Bonferroni) associated with RA, including the previously reported metabolites as DHEAS, cortisol and androstenedione and extending that to a larger set of metabolites in the steroid pathway. RA classification using metabolic profiles shows a sensitivity of 91% and specificity of 88%. Steroid levels show variation among the RA patients according to the corticosteroid treatment; lowest in those taking the treatment at the time of the study, higher in those who never took the treatment, and highest in those who took it in the past. Finally, the GGM reflects metabolite relations from the steroidogenesis pathway.

SUBMITTER: Yousri NA

PROVIDER: S-EPMC5567269 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Large Scale Metabolic Profiling identifies Novel Steroids linked to Rheumatoid Arthritis.

Yousri Noha A NA Bayoumy Karim K Elhaq Wessam Gad WG Mohney Robert P RP Emadi Samar Al SA Hammoudeh Mohammed M Halabi Hussein H Masri Basel B Badsha Humeira H Uthman Imad I Plenge Robert R Saxena Richa R Suhre Karsten K Arayssi Thurayya T

Scientific reports 20170822 1

Recent metabolomics studies of Rheumatoid Arthritis (RA) reported few metabolites that were associated with the disease, either due to small cohort sizes or limited coverage of metabolic pathways. Our objective is to identify metabolites associated with RA and its cofounders using a new untargeted metabolomics platform. Moreover, to investigate the pathomechanism of RA by identifying correlations between RA-associated metabolites. 132 RA patients and 104 controls were analyzed for 927 metabolite ...[more]

PMID: 28831053

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Project description:BackgroundBoar taint is observed in a high proportion of uncastrated male pigs and is characterized by an unpleasant odor/flavor in cooked meat, primarily caused by elevated levels of androstenone and skatole. Androstenone is a steroid produced in the testis in parallel with biosynthesis of other sex steroids like testosterone and estrogens. This represents a challenge when performing selection against androstenone in breeding programs, without simultaneously decreasing levels of other steroids. The aim of this study was to use high-density genome wide association (GWA) in combination with linkage disequilibrium-linkage analysis (LDLA) to identify quantitative trait loci (QTL) associated with boar taint compounds and related sex steroids in commercial Landrace (n = 1,251) and Duroc (n = 918) breeds.ResultsAltogether, 14 genome wide significant (GWS) QTL regions for androstenone in subcutaneous fat were obtained from the LDLA study in Landrace and 14 GWS QTL regions in Duroc. LDLA analysis revealed that 7 of these QTL regions, located on SSC 1, 2, 3, 7 and 15, were obtained in both breeds. All 14 GWS androstenone QTLs in Landrace are also affecting the estrogens at chromosome wise significance (CWS) or GWS levels, while in Duroc, 3 of the 14 QTLs affect androstenone without affecting any of the estrogens. For skatole, 10 and 4 QTLs were GWS in the LDLA analysis for Landrace and Duroc respectively, with 4 of these detected in both breeds. The GWS QTLs for skatole obtained by LDLA are located at SSC 1, 5, 6, 7, 10, 11, 13 and 14.ConclusionThis is the first report applying the Porcine 60 K SNP array for simultaneous analysis of boar taint compounds and related sex hormones, using both GWA and LDLA approaches. Several QTLs are involved in regulation of androstenone and skatole, and most of the QTLs for androstenone are also affecting the levels of estrogens. Seven QTLs for androstenone were detected in one breed and confirmed in the other, i.e. in an independent sample, although the majority of QTLs are breed specific. Most QTLs for skatole do not negatively affect other sex hormones and should be easier to implement into the breeding scheme.

Dataset Information

Large Scale Metabolic Profiling identifies Novel Steroids linked to Rheumatoid Arthritis.

Publications

Large Scale Metabolic Profiling identifies Novel Steroids linked to Rheumatoid Arthritis.

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