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.
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References
Burdge GC, Calder PC : Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults. Reprod Nutr Dev 2005; 45: 581–597.
Kris-Etherton PM, Harris WS, Appel LJ : Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002; 106: 2747–2757.
Williard DE, Nwankwo JO, Kaduce TL et al: Identification of a fatty acid delta6-desaturase deficiency in human skin fibroblasts. J Lipid Res 2001; 42: 501–508.
Nwankwo JO, Spector AA, Domann FE : A nucleotide insertion in the transcriptional regulatory region of FADS2 gives rise to human fatty acid delta-6-desaturase deficiency. J Lipid Res 2003; 44: 2311–2319.
Baylin A, Ruiz-Narvaez E, Kraft P, Campos H : alpha-Linolenic acid, Delta6-desaturase gene polymorphism, and the risk of nonfatal myocardial infarction. Am J Clin Nutr 2007; 85: 554–560.
Metcalf RG, James MJ, Mantzioris E, Cleland LG : A practical approach to increasing intakes of n-3 polyunsaturated fatty acids: use of novel foods enriched with n-3 fats. Eur J Clin Nutr 2003; 57: 1605–1612.
Schaeffer L, Gohlke H, Muller M et al: Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet 2006; 15: 1745–1756.
Lattka E, Eggers S, Moeller G et al: A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1. J Lipid Res 2010; 51: 182–191.
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This work was supported by the National Health and Medical Research Council of Australia and the Australian Research Council.
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Gregory, M., Lester, S., Cook-Johnson, R. et al. Fatty acid desaturase 2 promoter mutation is not responsible for Δ6-desaturase deficiency. Eur J Hum Genet 19, 1202–1204 (2011). https://doi.org/10.1038/ejhg.2011.104
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DOI: https://doi.org/10.1038/ejhg.2011.104
