1. 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

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

3. (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

4. 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

5. 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

6. 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 rs 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).

7. 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)

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

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

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

11. 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

12. 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

13. 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.

14. 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

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