title: 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.
authors.affiliation: Department of Mother and Child, and Biology-Genetics, Section of Biology and Genetics, University of Verona, Verona, Italy. giovanni.malerba@univr.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Malerba
authors.forename: Linda
authors.initials: L
authors.lastname: Schaeffer
authors.forename: Luciano
authors.initials: L
authors.lastname: Xumerle
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Trabetti
authors.forename: Michele
authors.initials: M
authors.lastname: Biscuola
authors.forename: Ugo
authors.initials: U
authors.lastname: Cavallari
authors.forename: Roberta
authors.initials: R
authors.lastname: Galavotti
authors.forename: Nicola
authors.initials: N
authors.lastname: Martinelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Guarini
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.forename: Oliviero
authors.initials: O
authors.lastname: Olivieri
authors.forename: Roberto
authors.initials: R
authors.lastname: Corrocher
authors.forename: Joachim
authors.initials: J
authors.lastname: Heinrich
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Pignatti
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
mesh_terms: D000368:Aged; D016718:Arachidonic Acid / Q000097:blood; D002318:Cardiovascular Diseases / Q000235:genetics*; D002462:Cell Membrane / Q000378:metabolism; D015331:Cohort Studies; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics*; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D005260:Female; D006801:Humans; D050602:Linoleoyl-CoA Desaturase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D005231:Fatty Acids, Unsaturated; D016718:Arachidonic Acid; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; D050602:Linoleoyl-CoA Desaturase