Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Branched chain amino acids (BCAA) are essential elements of the human diet, which display increased plasma levels in obesity and regained particular interest as potential biomarkers for development of diabetes. To define determinants of insulin resistance (IR) we investigated 73 genes involved in BCAA metabolism or regulation by fine-scale haplotype mapping in two European populations with metabolic syndrome. French and Romanians (n = 465) were genotyped for SNPs (Affymetrix) and enriched by imputation (BEAGLE 4.1) at 1000 genome project density. Initial association hits detected by sliding window were refined (HAPLOVIEW 3.1 and PHASE 2.1) and correlated to homeostasis model assessment (HOMAIR) index, in vivo insulin sensitivity (SI) and BCAA plasma levels (ANOVA). Four genomic regions were associated with IR located downstream of MUT, AACS, SLC6A15 and PRKCA genes (P between 9.3 and 3.7 x 10-5). Inferred haplotypes up to 13 SNPs length were associated with IR (e.g. MUT gene with P < 4.9 x 10-5; Bonferroni 1.3 x 10-3) and synergistic to HOMAIR. SNPs in the same regions were also associated with one order of magnitude lower P values (e.g. rs20167284 in the MUT gene with P < 1.27 x 10-4) and replicated in Mediterranean samples (n = 832). In French, influential haplotypes (OR > 2.0) were correlated with in vivo insulin sensitivity (1/SI) except for SLC6A15 gene. Association of these genes with BCAA levels was variable, but influential haplotypes confirmed implication of MUT from BCAA metabolism as well as a role of regulatory genes (AACS and PRKCA) and suggested potential changes in transcriptional activity. These data drive attention towards new regulatory regions involved in IR in relation with BCAA and show the ability of haplotypes in phased DNA to detect signals complimentary to SNPs, which may be useful in designing genetic markers for clinical applications in ethnic populations.
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PMID:Fine-scale haplotype mapping of MUT, AACS, SLC6A15 and PRKCA genes indicates association with insulin resistance of metabolic syndrome and relationship with branched chain amino acid metabolism or regulation. 3091 80

Improvement of feed efficiency (FE) is key for Sustainability and cost reduction in pig production. Our aim was to characterize the muscle transcriptomic profiles in Danbred Duroc (Duroc; n = 13) and Danbred Landrace (Landrace; n = 28), in relation to FE for identifying potential biomarkers. RNA-seq data on the 41 pigs was analyzed employing differential gene expression methods, gene-gene interaction and network analysis, including pathway and functional analysis. We also compared the results with genome regulation in human exercise data, hypothesizing that increased FE mimics processes triggered in exercised muscle. In the differential expression analysis, 13 genes were differentially expressed, including: MRPS11, MTRF1, TRIM63, MGAT4A, KLH30. Based on a novel gene selection method, the divergent count, we performed pathway enrichment analysis. We found five significantly enriched pathways related to feed conversion ratio (FCR). These pathways were mainly related to mitochondria, and summarized in the mitochondrial translation elongation (MTR) pathway. In the gene interaction analysis, the most interesting genes included the mitochondrial genes: PPIF, MRPL35, NDUFS4 and the fat metabolism and obesity genes: AACS, SMPDL3B, CTNNBL1, NDUFS4, and LIMD2. In the network analysis, we identified two modules significantly correlated with FCR. Pathway enrichment of module genes identified MTR, electron transport chain and DNA repair as enriched pathways. The network analysis revealed the mitochondrial gene group NDUF as key network hub genes, showing their potential as biomarkers. Results show that genes related to human exercise were enriched in identified FCR related genes. We conclude that mitochondrial activity is a key driver for FCR in muscle tissue, and mitochondrial genes could be potential biomarkers for FCR in pigs.
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PMID:Genome Regulation and Gene Interaction Networks Inferred From Muscle Transcriptome Underlying Feed Efficiency in Pigs. 3265 25