Intake of n-3 polyunsaturated fatty acids in childhood, FADS genotype and incident asthma

Abstract

Longitudinal evidence on the relation between dietary intake of n-3 (ω-3) very-long-chain polyunsaturated fatty acids, i.e. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mid-childhood and asthma risk is scarce. We aimed to investigate whether a higher intake of EPA and DHA from fish in childhood is associated with a lower risk of incident asthma.In the Avon Longitudinal Study of Parents and Children, dietary intakes of EPA and DHA from fish were estimated by food frequency questionnaire at 7 years of age. We used logistic regression, controlling for confounders, to analyse associations between intake of EPA and DHA (quartiles) and incidence of doctor-diagnosed asthma at age 11 or 14 years, and explored potential effect modification by a fatty acid desaturase (FADS) polymorphism (rs1535). Replication was sought in the Swedish BAMSE birth cohort.There was no evidence of association between intake of EPA plus DHA from fish and incident asthma overall (n=4543). However, when stratified by FADS genotype, the odds ratio comparing the top versus bottom quartile among the 2025 minor G allele carriers was 0.49 (95% CI 0.31-0.79; p_trend=0.006), but no inverse association was observed in the homozygous major A allele group (OR 1.43, 95% CI 0.83-2.46; p_trend=0.19) (p_interaction=0.006). This gene-nutrient interaction on incident asthma was replicated in BAMSE.In children with a common FADS variant, higher intake of EPA and DHA from fish in childhood was strongly associated with a lower risk of incident asthma up to mid-adolescence.

FIGURE 1

Directed acyclic graph to study covariates and potential structural confounding bias for the association between child's fish intake at 7 years and incident asthma risk. SES: socioeconomic status; BMI: body mass index; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid.

FIGURE 2

Dose–response relationship between eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) from fish and risk of incident asthma a) overall, b) in those homozygous for the major A allele and c) in carriers of the minor G allele using restricted cubic spline analysis in the Avon Longitudinal Study of Parents and Children. The model was adjusted for sex, total energy intake at 7 years, maternal education, housing tenure during pregnancy, financial difficulty during pregnancy, maternal ethnicity, maternal history of atopic disease, maternal age at delivery, exclusive breastfeeding, childcare by day nursery at 15 months of age, maternal smoking, older sibling, younger sibling and season when the food frequency questionnaire was completed. 56.3% of children were in the rs1535 GA/GG genotype group. The range of EPA plus DHA intake from fish was 0–675 mg·day⁻¹ with skewness, so this was truncated for presentation purposes.