Effect of the PPAR-Alpha L162V polymorphism on the cardiovascular disease risk factor in response to n-3 polyunsaturated fatty acids.
BACKGROUND
Dietary n-3 polyunsaturated fatty acids (PUFAs) decrease the risk of cardiovascular disease (CVD). Yet, genetic variations of the gene encoding the peroxisome proliferator-activated receptor-alpha (PPARalpha) can also modulate CVD risk factors. Since fatty acids, including n-3 PUFAs, are natural ligands of PPARalpha, a gene-diet interaction effect could be observed.


OBJECTIVE
To examine whether n-3 PUFA- induced changes in CVD risk factors are influenced by the PPARalpha L162V polymorphism.


METHODS
Fourteen men, carriers of the V162 allele and 14 L162 homozygotes, were matched according to age and body mass index. Subjects followed, for 8 weeks, a low-fat diet and then were supplemented daily with 5 g of fish oil for 6 weeks.


RESULTS
Baseline characteristics were similar for both genotype groups. Independently of the genotype, the supplementation was associated with a significant decrease in plasma triacylglycerol and fasting glucose concentrations, diastolic blood pressure, and with an increase in total apolipoprotein B concentrations. The extent of the decrease in plasma triacylglycerol concentrations was comparable for both genotype groups (p < 0.03). A significant genotype-by-diet interaction effect was observed for plasma C-reactive protein concentrations (p = 0.01).


CONCLUSIONS
The PPARalpha L162V polymorphism may contribute to the interindividual variability in the CVD risk factor response to n-3 PUFAs.
Caron-Dorval
Dominique
D
Lipid Research Center, CHUQ-CHUL Pavilion, Québec, Canada.
Paquet
Pascale
P
Paradis
Ann-Marie
AM
Rudkowska
Iwona
I
Lemieux
Simone
S
Couture
Patrick
P
Vohl
Marie-Claude
MC
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects*; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007930:Leucine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012307:Risk Factors; D014633:Valine / Q000235:genetics; D055815:Young Adult
D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D047493:PPAR alpha; D007930:Leucine; D014633:Valine