Long chain polyunsaturated fatty acids in serum phospholipids - relation to genetic polymorphisms, diet and allergy development in children

Doctoral thesis, 2015

Polyunsaturated fatty acids (PUFAs) are essential for human cell and tissue development. In foetus, PUFAs are supplied via placental transfer from maternal circulation. After birth, PUFAs are supplied via the diet. Long chain PUFAs (LCPUFAs) may also be synthesized from precursor fatty acids present in the diet. LCPUFAs have modulatory effects on the immune system. As maturation of the immune system in the neonatal period appears to be crucial for protection against allergy development, a major aim of the study was to study the impact of fatty acid composition in infant blood at birth on allergy development. Secondly, we sought to elucidate the sources of infant LCPUFAs with focus on polymorphisms in genes responsible for production of LCPUFAs in the body from shorter dietary fatty acids. Third, we studied whether LCPUFA and vitamin D metabolism differed in allergic and non-allergic adolescents. High proportions of either n-6 or n-3 LCPUFAs, among cord serum phospholipids were positively associated with the risk of developing either respiratory allergy, or atopic eczema, diagnosed at 13 years of age. We hypothesized that LCPUFAs counteract activation of the infant’s immune system in response to microbial stimuli in early life, thereby hampering the proper immune maturation necessary for healthy immune development. Regarding determinants of cord serum LCPUFA composition, we found that single nucleotide polymorphisms in the FADS gene cluster affected the proportion of the main n-6 LCPUFA, arachidonic acid, in cord serum as well as in adolescent serum. FADS gene polymorphisms that were associated with decreased proportions of arachidonic acid were also associated with a low prevalence of atopic eczema. Increased proportions of the n-3 LCPUFAs DPA and DHA in cord serum phospholipids were instead related to increased length of pregnancy. Adolescents with established allergy did not differ from non-allergic controls regarding proportions of LCPUFAs in serum phospholipids. Nor did they differ in vitamin D status. Proportions of n-3 LCPUFA in serum reflected dietary intake of fish in non-allergic adolescents, but not in adolescents with atopic eczema. The results may suggest that subjects with atopic eczema have a different LCPUFA metabolism, maybe because of enhanced usage of LCPUFAs during the allergic inflammation. In conclusion, the results suggest that LCPUFA metabolism may affects the risk of allergy development and may also be altered as a result of the allergic state. The lack of relation between allergy and vitamin D status in adolescents does not exclude that neonatal vitamin D status may affect allergy development.