Juan de Toro-Martín1, Frédéric Guénard1, Iwona Rudkowska2, Simone Lemieux1, Patrick Couture3, Marie-Claude Vohl4. 1. Institute of Nutrition and Functional Foods (INAF), Laval University, Quebec City, QC, Canada; School of Nutrition, Laval University, Quebec City, QC, Canada. 2. Endocrinology and Nephrology unit, Centre de recherche du CHU de Québec, Laval University, Quebec City, QC, Canada. 3. Institute of Nutrition and Functional Foods (INAF), Laval University, Quebec City, QC, Canada; Endocrinology and Nephrology unit, Centre de recherche du CHU de Québec, Laval University, Quebec City, QC, Canada. 4. Institute of Nutrition and Functional Foods (INAF), Laval University, Quebec City, QC, Canada; School of Nutrition, Laval University, Quebec City, QC, Canada. Electronic address: marie-claude.vohl@fsaa.ulaval.ca.
Abstract
BACKGROUND: Numbers of single nucleotide polymorphisms (SNPs) associated with fatty acid desaturase activities have been previously identified within the FADS1-FADS2 gene cluster, which encodes delta-5 (D5D) and delta-6 (D6D) desaturases, respectively. OBJECTIVE: We aimed at further characterizing the genetic variability associated with D5D and D6D activities on a genome-wide scale. METHODS: We conducted a genome-wide association study of D5D and D6D activities in a cohort of 141 individuals from the greater Quebec City metropolitan area using the Illumina HumanOmni5-Quad BeadChip. Estimates of D5D and D6D activities were computed using product-to-precursor fatty acid ratios, arachidonic acid (AA)/dihomo-gamma-linolenic acid (DGLA) for D5D, and DGLA/linoleic acid (LA) for D6D. Levels of fatty acids were measured by gas chromatography in plasma phospholipids. RESULTS: We identified 24 previously reported SNPs associated with fatty acid levels and desaturase activities as significantly associated with D5D activity within the FADS1-FADS2 gene cluster (lead SNP rs174566/A>G). Furthermore, we identified 5 novel loci potentially associated with D5D activity at chromosomes 1, 6, 4, 8 and 19. A novel SNP associated with D6D activity and mapped to the ARHGEF10 locus (rs2280885/A>G) was identified, with carriers of the rare allele showing a significant increase in D6D activity and plasma triglyceride levels. After multiple testing correction by permutation, only rs174566 and rs2280885 remained significantly associated to D5D and D6D activity estimates, respectively. CONCLUSIONS: These results confirm previous genetic associations within the FADS1-FADS2 gene cluster with D5D activity. A novel genetic variation associated with higher D6D activity within the ARHGEF10 gene is potentially altering plasma triglyceride levels.
BACKGROUND: Numbers of single nucleotide polymorphisms (SNPs) associated with fatty acid desaturase activities have been previously identified within the FADS1-FADS2 gene cluster, which encodes delta-5 (D5D) and delta-6 (D6D) desaturases, respectively. OBJECTIVE: We aimed at further characterizing the genetic variability associated with D5D and D6D activities on a genome-wide scale. METHODS: We conducted a genome-wide association study of D5D and D6D activities in a cohort of 141 individuals from the greater Quebec City metropolitan area using the Illumina HumanOmni5-Quad BeadChip. Estimates of D5D and D6D activities were computed using product-to-precursor fatty acid ratios, arachidonic acid (AA)/dihomo-gamma-linolenic acid (DGLA) for D5D, and DGLA/linoleic acid (LA) for D6D. Levels of fatty acids were measured by gas chromatography in plasma phospholipids. RESULTS: We identified 24 previously reported SNPs associated with fatty acid levels and desaturase activities as significantly associated with D5D activity within the FADS1-FADS2 gene cluster (lead SNP rs174566/A>G). Furthermore, we identified 5 novel loci potentially associated with D5D activity at chromosomes 1, 6, 4, 8 and 19. A novel SNP associated with D6D activity and mapped to the ARHGEF10 locus (rs2280885/A>G) was identified, with carriers of the rare allele showing a significant increase in D6D activity and plasma triglyceride levels. After multiple testing correction by permutation, only rs174566 and rs2280885 remained significantly associated to D5D and D6D activity estimates, respectively. CONCLUSIONS: These results confirm previous genetic associations within the FADS1-FADS2 gene cluster with D5D activity. A novel genetic variation associated with higher D6D activity within the ARHGEF10 gene is potentially altering plasma triglyceride levels.
Authors: Nicolo P P Macciotta; Licia Colli; Alberto Cesarani; Paolo Ajmone-Marsan; Wai Y Low; Rick Tearle; John L Williams Journal: Genet Sel Evol Date: 2021-02-27 Impact factor: 4.297
Authors: Susanne Jäger; Rafael Cuadrat; Per Hoffmann; Clemens Wittenbecher; Matthias B Schulze Journal: Nutrients Date: 2020-07-28 Impact factor: 5.717