Gene–Vitamin D Interactions on Food Sensitization: A Prospective Birth Cohort Study

Abstract

To explore the relationship of vitamin D deficiency and food sensitization, by investigating whether cord blood vitamin D deficiency is associated with food sensitization and whether such an association can be modified by genetic variants in a prospective birth cohort study.Children (N = 649) enrolled at birth in the Boston Birth Cohort and followed prospectively were studied. Children were included if data were available for cord blood 25(OH)D concentration, specific immunoglobulin E (IgE) to common food allergens, and genotyping of 11 candidate genes involved in regulation of either IgE or 25(OH)D concentrations.Vitamin D deficiency was defined as 25(OH)D <11 ng/mL, and food sensitization was defined as specific IgE ≥0.35 kUA/L to any of 8 common food allergens (milk, egg white, peanut, soy, shrimp, walnut, cod fish, and wheat) in early childhood. Genotyping for single nucleotide polymorphisms was done for 11 genes known to be involved in regulating 25(OH)D and IgE concentrations. The effects of vitamin D deficiency on food sensitization individually and jointly with single-nucleotide polymorphisms (SNPs) of the selected genes were tested by using logistic regression.Among the 649 children studied, 44% had vitamin D deficiency and 37% were food sensitized. Vitamin D deficiency was not associated with food sensitization when examined alone. When examined together with candidate gene SNPs, a significant interaction was detected between IL4 gene polymorphism (rs2243250) and vitamin D deficiency. Similar but weaker interactions were observed for SNPs in MS4A2 (rs512555), FCER1G (rs2070901), and CYP24A1 (rs2762934). The interaction between vitamin D deficiency and these polymorphisms was stronger when all 4 were considered together as opposed to individually.Vitamin D deficiency is associated with food sensitization in individuals with specific genotypes, suggesting an interaction between these features and food sensitization.The relationship between vitamin D deficiency and allergy has been an active area of research, and this study may help to explain conflicting findings from previous studies. These findings suggest that early vitamin D status may play a role in the development of food sensitization and subsequent food allergy in certain subpopulations with defined genetic susceptibilities. Future work, if confirmatory, could ultimately lead to better risk assessment and potential interventions for food allergy in early childhood.