Traditional Diet Influences Erythrocyte Fatty Acids Differentially Across Genetic Variants of Fatty Acid Metabolism: The Greenlandic Inuit Health in Transition Cohort (FS11-02-19)

Objectives: Traditional foods of the Greenlandic Inuit are mainly fish and marine mammals. Hence, the high fat content and unique dietary fatty acid (FA) profile may affect circulating FA profiles. Moreover, it is shown that the rs80356779 variant of the carnitine palmitoyl-transferase 1A (CPT1A) gene, involved in FA transportation, underwent positive selection in Inuit ancestors. The variant is associated with circulating FA profiles in Inuit, and selection may be a result of diet adaptation. While the variant may modify the dietary effect on FA metabolism, the gene-diet interaction has not been tested. Therefore, we aimed to assess if an interaction exists between the CPT1A variant and intake of traditional diet on erythrocyte membrane levels of very-long-chain n-3 PUFAs and the FAs previously found to be associated with the variant in Greenlandic Inuit.

Methods: We included 3005 individuals (mean age = 45 years) living in Greenland, who were genotyped and had erythrocyte membranes measured for the content of 40 FA. Food intake was estimated from a 68-item semi-quantitative food-frequency questionnaire. Consumption of 25 food items typical of the traditional diet was expressed as percentage of total energy intake. Linear mixed models were fitted, regressing a normalized FA variable on genotype, the Inuit diet variable, and their cross-product term, adjusting for population structure, relatedness, age, and sex. P-values were corrected by genomic control. Subsequent QQ-plots based on genome wide markers showed no indication of confounding.

Results: Sixty % of participants were homozygous for the derived CPT1A allele; 33% were heterozygous. Median % (interquartile range) of energy from traditional diet was 17% (8.8-30.5%). Of the 10 FAs that CPT1A had a main effect on (P < 10-5), significant diet × gene interactions (P < 0.001) were found for 20:1n-9, where the derived allele attenuated the positive association between diet and the FA, and for 20:3n-6, where the derived allele amplified the negative association between diet and the FA. Nominal effects (P < 0.05) were seen for 18:2n-6, 20:0, 24:0, and 22:5n-3.

Conclusions: Our results suggest the association between traditional diet and erythrocyte FA composition is affected by CPT1A genotype. Further analyses are needed to explore which specific foods drive the interaction.

Funding Sources: Lundbeck Foundation.