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Tissue-specific impact of FADS cluster variants on FADS1 and FADS2 gene expression.
PLoS One. 2018; 13(3):e0194610.Plos

Abstract

Omega-6 (n-6) and omega-3 (n-3) long (≥ 20 carbon) chain polyunsaturated fatty acids (LC-PUFAs) play a critical role in human health and disease. Biosynthesis of LC-PUFAs from dietary 18 carbon PUFAs in tissues such as the liver is highly associated with genetic variation within the fatty acid desaturase (FADS) gene cluster, containing FADS1 and FADS2 that encode the rate-limiting desaturation enzymes in the LC-PUFA biosynthesis pathway. However, the molecular mechanisms by which FADS genetic variants affect LC-PUFA biosynthesis, and in which tissues, are unclear. The current study examined associations between common single nucleotide polymorphisms (SNPs) within the FADS gene cluster and FADS1 and FADS2 gene expression in 44 different human tissues (sample sizes ranging 70-361) from the Genotype-Tissue Expression (GTEx) Project. FADS1 and FADS2 expression were detected in all 44 tissues. Significant cis-eQTLs (within 1 megabase of each gene, False Discovery Rate, FDR<0.05, as defined by GTEx) were identified in 12 tissues for FADS1 gene expression and 23 tissues for FADS2 gene expression. Six tissues had significant (FDR< 0.05) eQTLs associated with both FADS1 and FADS2 (including artery, esophagus, heart, muscle, nerve, and thyroid). Interestingly, the identified eQTLs were consistently found to be associated in opposite directions for FADS1 and FADS2 expression. Taken together, findings from this study suggest common SNPs within the FADS gene cluster impact the transcription of FADS1 and FADS2 in numerous tissues and raise important questions about how the inverse expression of these two genes impact intermediate molecular (such a LC-PUFA and LC-PUFA-containing glycerolipid levels) and ultimately clinical phenotypes associated with inflammatory diseases and brain health.

Authors+Show Affiliations

Department of Epidemiology & Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.Department of Internal Medicine/Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29590160

Citation

Reynolds, Lindsay M., et al. "Tissue-specific Impact of FADS Cluster Variants On FADS1 and FADS2 Gene Expression." PloS One, vol. 13, no. 3, 2018, pp. e0194610.
Reynolds LM, Howard TD, Ruczinski I, et al. Tissue-specific impact of FADS cluster variants on FADS1 and FADS2 gene expression. PLoS ONE. 2018;13(3):e0194610.
Reynolds, L. M., Howard, T. D., Ruczinski, I., Kanchan, K., Seeds, M. C., Mathias, R. A., & Chilton, F. H. (2018). Tissue-specific impact of FADS cluster variants on FADS1 and FADS2 gene expression. PloS One, 13(3), e0194610. https://doi.org/10.1371/journal.pone.0194610
Reynolds LM, et al. Tissue-specific Impact of FADS Cluster Variants On FADS1 and FADS2 Gene Expression. PLoS ONE. 2018;13(3):e0194610. PubMed PMID: 29590160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tissue-specific impact of FADS cluster variants on FADS1 and FADS2 gene expression. AU - Reynolds,Lindsay M, AU - Howard,Timothy D, AU - Ruczinski,Ingo, AU - Kanchan,Kanika, AU - Seeds,Michael C, AU - Mathias,Rasika A, AU - Chilton,Floyd H, Y1 - 2018/03/28/ PY - 2017/12/08/received PY - 2018/03/06/accepted PY - 2018/3/29/entrez PY - 2018/3/29/pubmed PY - 2018/7/25/medline SP - e0194610 EP - e0194610 JF - PloS one JO - PLoS ONE VL - 13 IS - 3 N2 - Omega-6 (n-6) and omega-3 (n-3) long (≥ 20 carbon) chain polyunsaturated fatty acids (LC-PUFAs) play a critical role in human health and disease. Biosynthesis of LC-PUFAs from dietary 18 carbon PUFAs in tissues such as the liver is highly associated with genetic variation within the fatty acid desaturase (FADS) gene cluster, containing FADS1 and FADS2 that encode the rate-limiting desaturation enzymes in the LC-PUFA biosynthesis pathway. However, the molecular mechanisms by which FADS genetic variants affect LC-PUFA biosynthesis, and in which tissues, are unclear. The current study examined associations between common single nucleotide polymorphisms (SNPs) within the FADS gene cluster and FADS1 and FADS2 gene expression in 44 different human tissues (sample sizes ranging 70-361) from the Genotype-Tissue Expression (GTEx) Project. FADS1 and FADS2 expression were detected in all 44 tissues. Significant cis-eQTLs (within 1 megabase of each gene, False Discovery Rate, FDR<0.05, as defined by GTEx) were identified in 12 tissues for FADS1 gene expression and 23 tissues for FADS2 gene expression. Six tissues had significant (FDR< 0.05) eQTLs associated with both FADS1 and FADS2 (including artery, esophagus, heart, muscle, nerve, and thyroid). Interestingly, the identified eQTLs were consistently found to be associated in opposite directions for FADS1 and FADS2 expression. Taken together, findings from this study suggest common SNPs within the FADS gene cluster impact the transcription of FADS1 and FADS2 in numerous tissues and raise important questions about how the inverse expression of these two genes impact intermediate molecular (such a LC-PUFA and LC-PUFA-containing glycerolipid levels) and ultimately clinical phenotypes associated with inflammatory diseases and brain health. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/29590160/Tissue_specific_impact_of_FADS_cluster_variants_on_FADS1_and_FADS2_gene_expression_ L2 - http://dx.plos.org/10.1371/journal.pone.0194610 DB - PRIME DP - Unbound Medicine ER -