Genetic variants of the fatty acid desaturase gene cluster predict amounts of red blood cell docosahexaenoic and other polyunsaturated fatty acids in pregnant women: findings from the Avon Longitudinal Study of Parents and Children

Background: Blood and tissue long-chain polyunsaturated fatty acid (LC-PUFA) amounts, which have been associated with early development and lifelong health, depend on dietary intake and endogenous conversion of precursor fatty acids (FAs) by the enzymes Delta(5)-desaturase and Delta(6)-desaturase. Polymorphisms in the desaturase encoding genes FADS1 and FADS2 have been associated with several n-6 (omega-6) and n-3 (omega-3) FAs and especially with arachidonic acid (AA) amounts. Associations with docosahexaenoic acid (DHA), which is considered particularly important for brain and retina development, are hardly existent. Objective: We explored the relation between FADS gene cluster polymorphisms and red blood cell (RBC) FA amounts in >4000 pregnant women participating in the Avon Longitudinal Study of Parents and Children. Design: Linear regression analysis of 17 single nucleotide polymorphisms (SNPs) in the FADS gene cluster was conducted with RBC phospholipid FAs from 6711 samples from 4457 women obtained throughout pregnancy (mean +/- SD gestational age: 26.8 +/- 8.2 wk). Results: Independent of dietary effects, the minor alleles were consistently positively associated with precursor FAs and negatively associated with LC-PUFAs and product: substrate ratios of the n-6 (AA: linoleic acid ratio) and n-3 (eicosapentaenoic acid: alpha-linolenic acid ratio) pathways. In contrast to previous studies, we also showed significant inverse associations with DHA. Similar but weaker associations were shown for the FADS3 SNP rs174455. Conclusions: FADS genotypes influence DHA amounts in maternal RBC phospholipids and might affect the child's DHA supply during pregnancy. It is highly likely that a gene product of FADS3 has a desaturating activity.