Human Molecular Genetics Advance Access originally published online on May 2, 2006
Human Molecular Genetics 2006 15(11):1745-1756; doi:10.1093/hmg/ddl117
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Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids
1GSF—National Research Center for Environment and Health, Institute of Epidemiology, 85764 Neuherberg, Germany, 2LMU-IBE, University of Munich, Department of Epidemiology, 81377 Munich, Germany, 3Western Australian Institute for Medical Research, University of Western Australia, 6009 Perth, Australia and 4Division of Metabolic Disorders and Nutrition, Dr von Haunersches Kinderspital, 80337 Munich, Germany
* To whom correspondence should be addressed at: GSF-Institute of Epidemiology, PO Box 1129, D-85758 Neuherberg, Germany. Tel: +49 8931874150; Fax: +49 8931873380; Email: joachim.heinrich{at}gsf.de
Received March 1, 2006; Accepted April 4, 2006
Fatty acid composition in membranes plays an important role in cellular processes and has shown to be associated with the aetiology of several complex diseases in humans. We report strong associations between variants in the human delta-5 and delta-6 desaturase genes FADS1 FADS2 and fatty acid composition in serum phospholipids. Eighteen polymorphisms located in this gene cluster were genotyped in 727 adults from Erfurt, a German centre of the European Community Respiratory Health Survey. The cluster is located at chromosome 11q12–11q13.1, a region repeatedly found to be linked with atopy and other complex diseases. Polymorphisms and statistically reconstructed haplotypes of FADS1 and the upstream region of FADS2 showed strongest associations with the level of the direct precursor of inflammatory eicosanoids, the n-6 fatty acid arachidonic acid (C20:4n-6), also strong associations with levels of the n-6 fatty acids C18:2n-6, C18:3n-6, C20:2n-6, C20:3n-6, C22:4n-6 and of the n-3 fatty acids C18:3n-3, C20:5n-3 and C22:5n-3 (P-values <1.0x10–13). Carriers of the rare alleles of several SNPs and their respective haplotypes had a lower prevalence of allergic rhinitis and atopic eczema. No association was found for total and specific IgE levels.
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