British Journal of Nutrition

Full Papers

Molecular Nutrition

Genetic variation of the FADS1 FADS2 gene cluster and n-6 PUFA composition in erythrocyte membranes in the European Prospective Investigation into Cancer and Nutrition-Potsdam study

Vera Zietemanna1, Janine Krögera2a3, Cornelia Enzenbacha1, Eugene Jansena4, Andreas Fritschea5, Cornelia Weikerta2a6, Heiner Boeinga2 and Matthias B. Schulzea1a2a3 c1

a1 Public Health Nutrition Unit, Technische Universität München, Freising, Germany

a2 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

a3 Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany

a4 Laboratory for Health Protection Research, National Institute for Public Health and The Environment, Bilthoven, The Netherlands

a5 Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germany

a6 Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medicine Berlin, Germany


Delta-5 (D5D) and delta-6 (D6D) desaturases are key enzymes in PUFA metabolism. Several factors (e.g. hyperglycaemia, hypertension, blood lipids, statins and fatty acids in diet and biological tissues) may influence desaturase activity. The goals were to evaluate the associations between variation in genes encoding these desaturases (FADS1 and FADS2) and blood concentrations of n-6 PUFA and estimated D5D and D6D activities (evaluated as product/precursor ratio), and to investigate whether other factors influencing the activity of desaturases modify these associations. A random sample of 2066 participants from the European Prospective Investigation into Cancer and Nutrition-Potsdam study (n 27 548) was utilised in the analyses. Crude and adjusted associations between rs174546 genotypes (reflecting genetic variation in the FADS1 FADS2 gene cluster), n-6 PUFA in erythrocytes and estimated desaturase activities were evaluated using multiple linear regression. Potential effect modification was determined by performing stratified analyses and evaluating interaction terms. We found rs174546 genotypes to be related to linoleic (r2 0·060), γ-linolenic (r2 0·041), eicosadienoic (r2 0·034), arachidonic (r2 0·026), docosatetraenoic acids (r2 0·028), estimated D6D activity (r2 0·052) and particularly strongly to dihomo-γ-linolenic acid (DGLA, r2 0·182) and D5D activity (r2 0·231). We did not observe effect modifications with regard to the estimated D5D activity, DGLA and arachidonic acid (AA) for most of the factors evaluated; however, the genetic effect on D5D activity and DGLA may be modified by the dietary n-6:n-3-ratio (P-values for interaction: 0·008 and 0·002), and the genetic effect on DGLA and AA may be modified by lipid-lowering medication (P-values for interaction: 0·0004 and 0·006). In conclusion, genetic variation in the FADS1 FADS2 gene cluster affects n-6 PUFA profiles in erythrocytes reflecting altered D5D activity.

(Received February 17 2010)

(Revised June 23 2010)

(Accepted June 24 2010)

(Online publication August 09 2010)


c1 Corresponding author: M. B. Schulze, fax +49 33200 88 437, email


Abbreviations: AA, arachidonic acid; ALA, α-linolenic acid; CC, homozygote carrier of the major C-allele; CT, carrier of the minor T-allele; D5D, delta-5 desaturase; D6D, delta-6 desaturase; DGLA, dihomo-γ-linolenic acid; DTA, docosatetraenoic acid; EDA, eicosadienoic acid; GLA, γ-linolenic acid; LA, linoleic acid; LD, linkage disequilibrium