Key Findings:
A deletion in the promoter region of the Δ6-desaturase gene (FADS2) may affect the conversion of ALA and LA into long-chain PUFA. This could reduce the benefits of ALA in myocardial infarction. A common deletion in the FADS2 promoter was associated with low tissue EPA and AA. A modifying effect of the FADS2 deletion on the protective effect of ALA was not reported. A high intake of ALA and LA was found to down-regulate the Δ6-desaturase enzyme. Further research in populations with low intake of α-linolenic acid and very-long chain n-3 fatty acids is suggested.
ABSTRACT:
Δ6-Desaturase (FADS2) is the rate-limiting step in the polyunsaturated fatty acid (PUFA) biosynthetic pathway.The aim was to test whether the common deletion [T/-] in the promoter of FADS2 affects the PUFA biosynthetic pathway and consequently modifies the effect of α-linolenic acid (ALA) on myocardial infarction (MI). Case subjects (n= 1694) with a first nonfatal acute MI were matched by age, sex, and area of residence to 1694 population-based control subjects in Costa Rica. PUFAs were quantified by gas-liquid chromatography from plasma and adipose tissue samples. Least squares means from generalized linear models and odds ratios (ORs) and 95% CIs from multiple conditional logistic regression models were estimated.The prevalence of the variant T/- allele was 48%. Eicosapentaenoic acid, y-linolenic acid, and arachidonic acid decreased in adipose tissue and plasma with increasing number of copies of the variant allele with a monotonic trend (P< 0.05 for all). Fasting plasma triacylglycerols by genotype were 2.08 mmol/L for TT, 2.16 mmol/L for T-, and 2.26 mmol/L for – – [ie, homozygous for the variant (deletion) allele] (P= 0.03). The FADS2 deletion was not associated with MI and did not significantly modify the association between adipose tissue ALA and the risk of MI. The FADS2 deletion may prevent the conversion of ALA into very-long-chain PUFAs .However, this metabolic effect is not translated into an attenuated risk between ALA and MI among carriers of the variant. It is possible that, at current intakes of ALA, any potential defect in the transcription of the gene is masked by the availability of substrate. Further research in populations deficient in ALA intake is warranted. (Author’s abstract)