SNPs of the FADS Gene Cluster are Associated with Polyunsaturated Fatty Acids in a Cohort of Patients with Cardiovascular Disease

Abstract

Polymorphisms of the human Delta-5 (FADS1) and Delta-6 (FADS2) desaturase genes have been recently described to be associated with the level of several long-chain n-3 and n-6 polyunsaturated fatty acids (PUFAs) in serum phospholipids. We have genotyped 13 single nucleotide polymorphisms (SNPs) located on the FADS1-FADS2-FADS3 gene cluster (chromosome 11q12-13.1) in 658 Italian adults (78% males; mean age 59.7 +/- 11.1 years) participating in the Verona Heart Project. Polymorphisms and statistically inferred haplotypes showed a strong association with arachidonic acid (C20:4n-6) levels in serum phospholipids and in erythrocyte cell membranes (rs174545 adjusted P value for multiple tests, P < 0.0001 and P < 0.0001, respectively). Other significant associations were observed for linoleic (C18:2n-6), alpha-linolenic (C18:3n-3) and eicosadienoic (C20:2n-6) acids. Minor allele homozygotes and heterozygotes were associated to higher levels of linoleic, alpha-linolenic, eicosadienoic and lower levels of arachidonic acid. No significant association was observed for stearidonic (C18:4n-3), eicosapentaenoic (C20:5n-3) and docosahexaenoic (C22:6n-3) acids levels. The observed strong association of FADS gene polymorphisms with the levels of arachidonic acid, which is a precursor of molecules involved in inflammation and immunity processes, suggests that SNPs of the FADS1 and FADS2 gene region are worth studying in diseases related to inflammatory conditions or alterations in the concentration of PUFAs.

Current status on genome–metabolome-wide associations: an opportunity in nutrition research

“…In addition, glycerophospholipids carrying less than 4 unsaturated bonds in their fatty acid chains are increased in individuals who carry the less efficient variant of FADS1, while sphingomyelins are decreased, suggesting a modification in phosphatidylcholines' homeostasis. These observations not only constituted a full replication of the association of this locus with arachidonic acid metabolism as previously reported (Schaeffer et al 2006;Malerba et al 2008), but also underpinned changes in the efficiency of the delta-5 desaturase reaction. This study further demonstrated that metabolic phenotype characterization can be improved by the use of ratios of metabolite concentrations.…”

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

“…In the Doetinchem Cohort Study, it was concluded that dietary intakes of n-3 and n-6 PUFA interact with FADS1 polymorphism to affect plasma total and HDL-cholesterol levels 166 . In populations consuming a Western diet, it has been shown that the FADS polymorphism which is associated with higher desaturase activity may result in higher risk of proinflammatory response, and thus, atherosclerosis 167,168 . Also, carriers of the rare allele of FADS SNP and their haplotypes had altered eicosanoid precursor levels and a lower prevalence of allergic disease and topical eczema 169 .…”

Polyunsaturated Fatty Acids, Ulcerative Colitis and Cancer Prevention

“…The hypothesis that they play a key role in inflammatory diseases is strengthened by functional studies in mice, where selective D5D and D6D inhibitors showed an anti-inflammatory response. Several single nucleotide polymorphisms (SNP) in FADS genes were reported in humans, and some showed association between FADS SNPs and fatty acids in serum or plasma phospholipids, and erythrocyte membrane and adipose tissue (Schaeffer et al 2006, Malerba et al 2008, Rzehak et al 2009), demonstrating that these concentrations are influenced not only by diet, but also to a large extent by genetic variants common in the world population (Koletzko et al 2011).…”