A common deletion in the promoter of the delta-6 desaturase gene is associated with high plasma triglycerides and low arachidonic acid and EPA in tissues
Artículo académicoRol de miembro
We studied 1384 population-based free-living Costa Ricans to examine a common deletion [T/-] in the promoter of the delta-6 desaturase gene (FADS2) that may affect the efficiency of conversion of linoleic and alpha-linolenic acid (ALA) into long-chain PUFA. Subjects completed a food-frequency questionnaire and donated blood and adipose tissue samples. PUFA from adipose tissue (N=1384) and plasma (N=200) were quantified by gas-liquid chromatography. Least square means from generalized linear models adjusted for potential confounders were used to estimate the association between FADS2 genotypes and plasma triglycerides, adipose tissue and plasma PUFA. The prevalence of the variant allele was 49.2%. Adipose tissue PUFA for homozygous for the wild type [TT], heterozygous [T −], and homozygous for the mutant [− −] were (% total FA): 0.52, 0.47, and 0.41 for arachidonic acid (p<0.0001), and 0.0389, 0.0386, and 0.0333 for EPA (p<0.0001). Similarly, in plasma they were 7.32, 6.03, and 4.46 for arachidonic acid (p<0.0001), and 0.49, 0.35, and 0.30 for EPA (N=63, p=0.06). On the other hand, adipose tissue and plasma 20:3n-3 and 20:2n-6 increased with the number of deletions (p-value <0.05 for all comparisons). Plasma triglycerides by genotype were 138 mg/dL, 147 mg/dL, and 155 mg/dL (p=0.036), after adjusting for intake of ALA, EPA, DHA, and other potential confounders. Our data suggest that the FADS2 deletion prevents the conversion of linoleic and ALA to long chain PUFA by decreasing the activity of delta-6 desaturase. The inverse association of FADS2 with 20:2n-6 and 20:3n-3 suggests an increased elongation of linoleic acid and ALA to these fatty acids, which represent dead-end products in the biosynthetic PUFA pathway. Because of its association with higher plasma triglycerides this common polymorphism may increase the risk of CHD.
