title: Fatty acid desaturase 2 promoter mutation is not responsible for Δ6-desaturase deficiency.
abstract: Dietary essential polyunsaturated fatty acids (PUFAs) require fatty acid desaturases (FADS) for conversion to long-chain PUFAs (LCPUFAs), which are critical for many aspects of human health. A Δ6-desaturase deficiency in a single patient was attributed to an insertion mutation in the FADS2 promoter. Later population studies have shown this thymidine nucleotide (T) insertion to be a common polymorphism (rs3834458). We examined correlations between rs3834458 variants and fatty acid evidence of FADS2 activity in a cohort of rheumatoid arthritis patients selected for low or nil consumption of n-3 LCPUFA as fish or fish oil. The presence of the T allele was associated with higher FADS2 activity, as indicated by higher conversion of plasma n-3 PUFA to LCPUFA. However, the T-insertion/deletion polymorphism did not affect FADS2 promoter activity in luciferase reporter assays in HepG2 or NIH/3T3 cells. Our results indicate that the polymorphism rs3834458 does not appear to directly affect FADS2 promoter activity and is not responsible for a previously reported Δ6-desaturase deficiency.
authors.affiliation: Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. melissa.gregory@health.sa.gov.au
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Gregory
authors.forename: Susan E
authors.initials: SE
authors.lastname: Lester
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cook-Johnson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gibson
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Proudman
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Cleland
authors.forename: Michael J
authors.initials: MJ
authors.lastname: James
mesh_terms: D000483:Alleles; D000818:Animals; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D056945:Hep G2 Cells; D006801:Humans; D050602:Linoleoyl-CoA Desaturase / Q000172:deficiency*; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012213:Rheumatic Fever / Q000235:genetics
chemical_list: D044943:Fatty Acid Desaturases; C533241:FADS2 protein, human; D050602:Linoleoyl-CoA Desaturase