FADS1 (Fatty Acid Desaturase 1) Genotype Associates With Aortic Valve FADS mRNA Expression, Fatty Acid Content and Calcification

• Published in: Circulation. Genomic and precision medicine Vol. 13; no. 3; p. e002710
• Main Authors: Plunde, Oscar, Larsson, Susanna C., Artiach, Gonzalo, Thanassoulis, George, Carracedo, Miguel, Franco-Cereceda, Anders, Eriksson, Per, Bäck, Magnus
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01-06-2020; Lippincott Williams & Wilkins
• Subjects: aortic valve; fatty acid desaturases; lipidomics; Medicin och hälsovetenskap; Original; polymorphism; quantitative trait loci; single nucleotide; expression quantitative trait loci; omega3 fatty acids
• ISSN: 2574-8300; 2574-8300
• DOI: 10.1161/CIRCGEN.119.002710

- Aortic stenosis (AS) contributes to cardiovascular mortality and morbidity but disease mechanisms remain largely unknown. Recent evidence associates a single nucleotide polymorphism rs174547 within the
gene, encoding fatty acid desaturase 1, with risk of several cardiovascular outcomes, including AS.
encodes a rate-limiting enzyme for ω-3 and ω-6 fatty acid metabolism. The aim of this study was to decipher the local transcriptomic and lipidomic consequences of rs174547 in tricuspid aortic valves from AS patients.
- Expression quantitative trait loci (eQTL) study was performed using data from Illumina Human610-Quad BeadChip, Infinium Global Screening Arrays, and Affymetrix Human Transcriptome 2.0 arrays in calcified and non-calcified aortic valve tissue from 58 AS patients (mean age 74.2, SD 5.9). Fatty acid content was assessed in aortic valves from 25 AS patients using gas chromatography. Δ5 and Δ6 desaturase activity was assessed by the product-to-precursor ratio.
- The minor C-allele of rs174547, corresponding to the protective genotype for AS, was associated with higher FADS2 mRNA levels in calcified valve tissue, whereas FADS1 mRNA and other transcripts in proximity of the SNP were unaltered. In contrast, the FADS1 Δ5-desaturase activity and the FADS2 Δ6-desaturase activity were decreased. Finally, docosahexaenoic acid (DHA) was decreased in calcified tissue compared to non-calcified tissue and C-allele carriers exhibited increased DHA levels. Overall desaturase activity measured with ω-3 fatty acids was higher in C-allele carriers.
- The association between the FADS1 genotype and AS may implicate effects on valvular fatty acids.