دورية أكاديمية
أعرض في EDS

Insertion-deletions in a FADS2 intron 1 conserved regulatory locus control expression of fatty acid desaturases 1 and 2 and modulate response to simvastatin.

التفاصيل البيبلوغرافية
العنوان: Insertion-deletions in a FADS2 intron 1 conserved regulatory locus control expression of fatty acid desaturases 1 and 2 and modulate response to simvastatin.
المؤلفون: Reardon HT; Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA., Zhang J, Kothapalli KS, Kim AJ, Park WJ, Brenna JT
المصدر: Prostaglandins, leukotrienes, and essential fatty acids [Prostaglandins Leukot Essent Fatty Acids] 2012 Jul; Vol. 87 (1), pp. 25-33. Date of Electronic Publication: 2012 Jun 27.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Churchill Livingstone Country of Publication: Scotland NLM ID: 8802730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-2823 (Electronic) Linking ISSN: 09523278 NLM ISO Abbreviation: Prostaglandins Leukot Essent Fatty Acids Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Edinburgh ; New York : Churchill Livingstone, c1988-
مواضيع طبية MeSH: Gene Expression Regulation* , INDEL Mutation*, Fatty Acid Desaturases/*genetics , Gene Expression/*drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology , Simvastatin/*pharmacology, Base Sequence ; Benzoates/pharmacology ; Benzylamines/pharmacology ; Binding Sites ; Cells, Cultured ; Conserved Sequence ; Delta-5 Fatty Acid Desaturase ; Gene Frequency ; Haplotypes ; Heterozygote ; Humans ; Introns ; Linkage Disequilibrium ; Liver X Receptors ; Locus Control Region ; Multigene Family ; Oligonucleotide Array Sequence Analysis ; Orphan Nuclear Receptors/agonists ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Response Elements ; Rosiglitazone ; Sequence Analysis, DNA ; Sterol Regulatory Element Binding Protein 1/agonists ; Sterol Regulatory Element Binding Protein 1/metabolism ; Thiazolidinediones/pharmacology
مستخلص: The fatty acid desaturase genes (FADS1 and FADS2) code for enzymes required for synthesis of omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFA) important in the central nervous system, inflammatory response, and cardiovascular health. SNPs in these genes are associated with numerous health outcomes, but it is unclear how genetic variation affects enzyme function. Here, lymphoblasts obtained from Japanese participants in the International HapMap Project were evaluated for association of expression microarray results with SNPs in the FADS gene cluster. Six SNPs in the first intron of the FADS2 gene were associated with FADS1 expression. A 10-SNP haplotype in FADS2 (rs2727270 to rs2851682) present in 24% of the population was associated with lower expression of FADS1. A highly conserved region coinciding with the most significant SNPs contained predicted binding sites for SREBP and PPARγ. Lymphoblasts homozygous for either the major or minor haplotype were treated with agonists for these transcription factors and expression of FADS1 and FADS2 determined. Simvastatin and the LXR agonist GW3965 both upregulated expression of FADS1 and FADS2; no response was found for PPARγ agonist rosiglitazone. The minor haplotype homozygotes had 20-40% higher induction of FADS1 and FADS2 after simvastatin or GW3965 treatment. A 22 bp polymorphic insertion-deletion (INDEL) was found 137 bp downstream from the putative sterol response element, as well as a 3 or 1 bp INDEL 81-83 bp downstream. All carriers of the minor haplotype had deletions while all carriers of the major haplotype had insertions. Individuals carrying the minor haplotype may be vulnerable to alterations in diet that reduce LCPUFA intake, and especially responsive to statin or marine oil therapy.
(Copyright © 2012 Elsevier Ltd. All rights reserved.)
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معلومات مُعتمدة: T32 HD052471 United States HD NICHD NIH HHS; T32HD052471 United States HD NICHD NIH HHS
المشرفين على المادة: 0 (Benzoates)
0 (Benzylamines)
0 (Delta-5 Fatty Acid Desaturase)
0 (GW 3965)
0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
0 (Liver X Receptors)
0 (Orphan Nuclear Receptors)
0 (Sterol Regulatory Element Binding Protein 1)
0 (Thiazolidinediones)
05V02F2KDG (Rosiglitazone)
AGG2FN16EV (Simvastatin)
EC 1.14.19.- (Fatty Acid Desaturases)
EC 1.14.19.3 (FADS1 protein, human)
EC 1.14.19.3 (FADS2 protein, human)
تواريخ الأحداث: Date Created: 20120704 Date Completed: 20130122 Latest Revision: 20211203
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC3404253
DOI: 10.1016/j.plefa.2012.04.011
PMID: 22748975
قاعدة البيانات: MEDLINE
الوصف
تدمد:1532-2823
DOI:10.1016/j.plefa.2012.04.011