Marie Standl Helmholtz Zentrum München Institute of Epidemiology I FADS1 FADS2 gene cluster, PUFA intake and blood lipids in children. Results from the GINIplus and LISAplus studies. Marie Standl Helmholtz Zentrum München Institute of Epidemiology I Bristol, 18/10/11

Cardiovascular diseases Background Dietary PUFA intake Total cholesterol High-density lipoprotein (HDL) Low-density lipoprotein (LDL) Triglycerides Cardiovascular diseases FADS Genes

(Docosahexaenoic acid) Fatty acid metabolism Omega 6 fatty acid Omega 3 fatty acid Major allele Minor allele FADS Genes More substrate AA (Arachidonic acid) DHA (Docosahexaenoic acid) “pro inflammatory” “beneficial effects” More product

Cardiovascular diseases Background Dietary PUFA intake Total cholesterol High-density lipoprotein (HDL) Low-density lipoprotein (LDL) Triglycerides Cardiovascular diseases Minor allele: Total cholesterol, HDL, LDL Triglycerides FADS Genes

Background Dietary PUFA intake Objective Are lipid levels already determined by the FADS genotype in school-aged children? Interaction between dietary PUFA intake and FADS genotype? Total cholesterol High-density lipoprotein (HDL) Low-density lipoprotein (LDL) Triglycerides FADS Genes

Methods Dietary n3 PUFA intake: Derived from FFQ (food frequency questionnaire) n3 PUFA = (ALA+EPA+DPA+DHA)/total dietary energy intake Results presented as mg/MJ per interquartile range increase FADS genes: six SNPs were genotyped (results presented for rs174556 and rs174575) Linear regression models: Total cholesterol, LDL, triglyceride: results presented as means ratios (log NV) HDL: results presented as estimate β and standard deviation (Sd) Adjustment: gender, study centre, age, BMI, fasting status and total dietary energy intake The n-3 PUFA intake was calculated by adding up the daily intake of α-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid (DPA, 22:5n-3) and docosahexaenoic acid (DHA, 22:6n-3).

Study population (with genetic information) % or Median (Qu. 25%/Qu. 75%) Study GINI 64% LISA 36% Fasting blood samples 18% Age [years] 10.2 (10.1/10.3) BMI [kg/m²] 17 (16/19) n-3 PUFA intake [mg/MJ] 0.14 (0.13/0.16) Total cholesterol [mmol/L] 4.79 (4.28/5.32) HDL [mmol/L] 1.24 (1.06/1.44) LDL [mmol/L] 2.12 (1.72/2.53) Triglyceride [mmol/L] 1.19 (0.90/1.64)

Results: Total cholesterol A: major allele / a: minor allele

Results: LDL A: major allele / a: minor allele

Results: Triglyceride A: major allele / a: minor allele

Results: HDL Estimate Sd p-value Estimate Sd p-value rs174556 n3 PUFA [mg/MJ] AA (ref) Aa (ref AA) aa (ref AA) Estimate 0.02 - -0.04 0.00 Sd 0.01 0.03 p-value 0.017 0.007 0.890 rs174575 n3 PUFA [mg/MJ] AA (ref) Aa (ref AA) aa (ref AA) Estimate 0.02 - -0.01 Sd 0.01 0.03 p-value 0.014 0.332 0.691 A: major allele / a: minor allele

Further results No interaction between n3 PUFA and FADS genotype No association between lipid levels and n6 PUFA intake Similar results for the n3 PUFAs ALA, EPA, DPA and DHA Similar results in a stratified analysis for LISA and GINI

Summary n3 PUFA: Total cholesterol, HDL and LDL Triglycerides Minor allele of FADS genotype: In conclusion: Total cholesterol, HDL, LDL and triglyceride concentrations are already determined by the FADS1 FADS2 genotype in 10 year old children. Genetically determined blood lipid levels during childhood might differentially predispose individuals to the development of cardiovascular diseases later in life.

Acknowledgements Eva Lattka Stefan Röder Barbara Stach Olf Herbarth Sibylle Koletzko Anette Buyken Carl-Peter Bauer Tim Drogies Andrea von Berg Joachim Thiery Dietrich Berdel Berthold Koletzko Ursula Krämer Joachim Heinrich Beate Schaaf

Characteristics of the FADS SNPs Results presented for rs174556 and rs174575 Genotype frequency aa aA AA rs174556 9% 41% 50% rs174575 7% 37% 56% a: minor allele A: major allele