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

Background

Cardiovascular diseases

• Total cholesterol

• High-density lipoprotein (HDL)

• Low-density lipoprotein (LDL)

• Triglycerides

Dietary PUFA intake

FADS Genes

Fatty acid metabolism

Omega 6fatty acid

AA(Arachidonic acid)

“pro inflammatory”

Omega 3fatty acid

DHA(Docosahexaenoic

acid)

“beneficial effects”

FADS Genes

Major allele

Minor allele

More product

More substrate

Background

Cardiovascular diseases

• Total cholesterol

• High-density lipoprotein (HDL)

• Low-density lipoprotein (LDL)

• Triglycerides

Dietary PUFA intake

FADS Genes

Minor allele:

Total cholesterol, HDL, LDL

Triglycerides

Background

• Total cholesterol

• High-density lipoprotein (HDL)

• Low-density lipoprotein (LDL)

• Triglycerides

Dietary PUFA intake

FADS Genes

Objective

• Are lipid levels already

determined by the

FADS genotype in

school-aged children?

• Interaction between

dietary PUFA intake

and FADS genotype?

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

Study population(with genetic information)

N=2006 % 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

rs174556 n3 PUFA [mg/MJ] AA (ref) Aa (ref AA) aa (ref AA)

Estimate 0.02 - -0.04 0.00

Sd 0.01 - 0.02 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 -0.01

Sd 0.01 - 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:

• Total cholesterol, HDL and LDL

• Triglycerides

Acknowledgements

Eva Lattka

Barbara Stach

Sibylle Koletzko

Carl-Peter Bauer

Andrea von Berg

Dietrich Berdel

Ursula Krämer

Beate Schaaf

Stefan Röder

Olf Herbarth

Anette Buyken

Tim Drogies

Joachim Thiery

Berthold Koletzko

Joachim Heinrich

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 alleleA: major allele