Children with nut allergies have impaired gene expression of Toll-like receptors pathway.

BACKGROUND: Trends in food allergies prompted investigation into the underlying mechanisms. Genetic and epigenetic factors are of high interest, and, in particular, the interplay between genes relating to immune factors directly and indirectly involved in food allergy pathogenesis. We sought to determine potential links between gene expression and epigenetic factors relating to Toll-like receptor (TLR) pathways and childhood food allergies. METHODS: In a cross-sectional study, samples from 80 children with and without food allergies were analysed for gene expression, DNA methylation and a range of immune factors relating to TLR pathways. TLR2, TLR4, CD14, IL5, IL13 and vitamin D were explored. RESULTS: The importance of these immune factors appeared to vary between the different types of food allergies. Expression of TLR2 (P < .001), TLR4 (P = .014) and CD14 (P = .028) varied significantly between children with no food allergy, allergy to nuts and peanuts, and allergy to eggs. DNA methylation in the promoter regions of these genes had a significant association with gene expression. These trends persisted when subjects were stratified by nut allergy vs no nut allergy. Furthermore, TLR2 (P = .001) and CD14 (P = .007) expressions were significantly lower in children with food allergies when compared to those without. CONCLUSION: Gene expression of TLR pathway genes was directly related to food allergy type, and DNA methylation had an indirect effect. TLR2 pathways are of significant interest in nut allergies.

Cord Blood IL-12 Confers Protection to Clinical Malaria in Early Childhood Life.

Using a well-designed longitudinal cohort, we aimed to identify cytokines that were protective against malaria and to explore how they were influenced by genetic and immunological factors. 349 Mozambican pregnant women and their newborn babies were recruited and followed up for malaria outcomes until 24 months of age. Six Th1 cytokines in cord blood were screened for correlation with malaria incidence, of which IL-12 was selected for further analyses. We genotyped IL-12 polymorphisms in children/mothers and evaluated the genotype-phenotype associations and genetic effects on IL-12 levels. Maternal IL-12 concentrations were also investigated in relation to Plasmodium infections and cord blood IL-12 levels. Our data showed that high background IL-12 levels were prospectively associated with a low incidence of clinical malaria, while IL-12 production after parasite stimulation had the opposite effect on malaria incidence. IL-12 genotypes (IL-12b rs2288831/rs17860508) and the haplotype CGTTAGAG distribution were related to malaria susceptibility and background IL-12 levels. Maternal genotypes also exhibited an evident impact on host genotype-phenotype associations. Finally, a positive correlation in background IL-12 levels between maternal and cord blood was identified. Thus, cord blood background IL-12 concentrations are important for protecting children from clinical malaria, likely mediated by both genotypes (children&mothers) and maternal immunity.

Cellular and molecular mechanisms of vitamin D in food allergy.

Food allergies are becoming increasingly prevalent, especially in young children. Epidemiological evidence from the past decade suggests a role of vitamin D in food allergy pathogenesis. Links have been made between variations in sunlight exposure, latitude, birth season and vitamin D status with food allergy risk. Despite the heightened interest in vitamin D in food allergies, it remains unclear by which exact mechanism(s) it acts. An understanding of the roles vitamin D plays within the immune system at the cellular and genetic levels, as well as the interplay between the microbiome and vitamin D, will provide insight into the importance of the vitamin in food allergies. Here, we discuss the effect of vitamin D on immune cell maturation, differentiation and function; microbiome; genetic and epigenetic regulation (eg DNA methylation); and how these processes are implicated in food allergies.

The Implications of DNA Methylation on Food Allergy.

Food allergy is a major clinical and public health concern worldwide. The risk factors are well defined, however, the mechanisms by which they affect immune development remain largely unknown, and unfortunately the effective treatment or prevention of food allergy is still being researched. Recent studies show that the genes that are critical for the development of food allergy are regulated through DNA methylation. Environmental factors can affect host DNA methylation status and subsequently predispose people to food allergy. DNA methylation is therefore an important mediator of gene-environment interactions in food allergy and key to understanding the mechanisms underlying the allergic development. Indeed, the modification and identification of the methylation levels of specific genetic loci have gained increasing attention for therapeutic and diagnostic application in combating food allergy. In this review, we summarize and discuss the recent developments of DNA methylation in food allergy, including the pathogenesis, therapy, and diagnosis. This review will also summarize and discuss the environmental factors that affect DNA methylation levels in food allergy.

Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes.

The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing either in the westernized environment of Denmark or in the rural area of Greenland. Our results showed that lung function was associated with genetic variants in ORMDL3, with polymorphisms having a significant interaction with place of residence. LT-α SNP rs909253 and rs1041981 were significantly associated with bronchitis risk. LT-α SNP rs2844484 was related to dermatitis susceptibility and was significantly influenced by the place of residence. The observed gene-phenotype relationships were exclusively present in one population and absent in the other population. We conclude that the genotype-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases.