科研之友
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摘要
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 ARH-GEF10 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.
- 出版日期2018-4
