Genetic risk score predicting the plasma triglyceride response
to either eicosapentaenoic or docosahexaenoic acid
Bastien Vallée Marcotte, Appl. Physiol. Nutr. Metab. Vol. 45, 2020 S52
Numerous studies have uncovered the contribution of genetic factors
to the heterogeneity of the plasma triglyceride (TG) response to an
omega-3 fatty acid (n-3 FA) supplementation. However, this genetic
contribution has never been investigated specifically for a supplementation to either eicosapentaenoic (EPA) or docosahexaenoic (DHA)
acid.
The objective of this study was to test the ability of a genetic risk
score (GRS), previously built to predict the plasma TG response to
combined EPA/DHA, can discriminate phenotypes of the plasma TG
response to independent supplementations of EPA or DHA. A total of
154 participants were randomly attributed to three different supplementation groups in a double-blind, controlled, crossover intervention:
1) 2.7 g/d of DHA,
2) 2.7 g/d of EPA and
3) 3 g/d of corn oil (control),
separated by 9-week washouts.
The TG response phenotypes were
defined as follows: positive responders (TG decrease following supplementation <0.25 mmol/L vs control), non-responders (TG variation
within ±0.25 mmol/L), and negative responders (TG increase vs
control >0.25 mmol/L). SNP selection was based on a previous GRS of the
TG response to n-3 FA supplementation developed by our group.
A total of 31 SNPs previously associated with the TG response were genotyped in 122 subjects using TaqMan technology. Ordinal and binary
logistic models, adjusted for age, sex and body mass index, were used
to calculate the ability of the GRS to discriminate phenotypes of TG
response. The GRS classified TG response phenotypes for EPA supplementation (odds ratio (OR)=1.2, p=0.006) and a trend was observed for
DHA supplementation (OR=1.2, p=0.08). Exclusion of non-responders
improved the significance of GRS predictions for both EPA (OR=2.3,
p=0.003) and DHA (OR=2.4, p=0.01).
In conclusion, these findings suggest
that the constructed GRS is an effective tool for predicting TG response
phenotypes following EPA or DHA supplementations