Prevalence Of Food Allergy In Jiangxi Province And The Effect Of VD And VD Metabolic Pathway Snp On Food Allergy

Adverse reaction to food is a major public health concern worldwide,among the various causes of the adverse reactions,food allergy is particularly serious,it is one of the most common causes of anaphylaxis.Food allergy affects about 5%adults and 8% children.Epidemiological studies have discovered that the prevalence of food allergy has been increasing globally over the last decades,and that the numbers of food groups causing allergies and anaphylaxis were also increasing.Food allergy can cause many physical and psychological disorders,severely affecting the quality of life of patients and their families,and imposing an increasing medical and economic burden on society.It has become a recognized global public health and food safety issue,with wide geographic variations in the incidence,types and clinical phenotypes.Currently,there is no national data on the prevalence of food allergy in China,but data from some small-scale surveys indicated that the prevalence of food allergy in China was also not optimistic;The development of food allergy is a complex process influenced by genetics,environment and geneenvironment interactions,the exact determinants remain largely speculative or unknown;Multifunctional vitamin D may affect the occurrence and development of food allergy through a variety of mechanisms,the immune mechanism has not been determined,and the gene polymorphism of vitamin D pathway may be associated with vitamin D status.Therefore,it is particularly important to conduct epidemiological studies on food allergy among the general population in China to explore the epidemic characteristics,influencing factors and possible mechanisms of food allergy,to provide a scientific basis for the development of effective prevention and control policies and measures of food allergy.This study was conducted to assess the prevalence and epidemiological characteristics of food allergy in the general population with reference to the Europrevall food allergy project,evaluate the association of food allergy and vitamin D,vitamin D metabolic pathway gene polymorphisms,and interactions between genes with vitamin D and other environmental factors on developing food allergies,explore specific pathways of FA pathogenesis and possible specific biomarkers of FA for implementing individualized food allergy prevention and treatment in precision medicine,provide reference basis for the effective prevention and management of local food allergy and the formulation of public health policies;also provide reference and experience for the epidemiological study on food allergy in other regions in China.The main methods,results and conclusions in this study were presented as following:1.A multicenter cross-sectional food allergy epidemiological study was conducted among the general population in Jiangxi Province using the optimized Euro Prevall food allergy questionnaire;Screening for food allergy was conducted with self-reported adverse reaction to food and food allergy.Samples of children aged 6-11 years were obtained from elementary school students in grades 1-5;adult samples were obtained from the community or natural villages.A total of 20,791 valid questionnaires were returned;Of them,5.8% reported adverse reactions to food and 4.3% reported food allergy.Children with self-reported adverse reactions to food screened in the first stage of the investigation and their controls were invited to undergo on-site questionnaires,physical examination and skin prick tests,and blood samples were taken and transported to the laboratory to test the relevant indexes.Clinical allergists determined the food allergy status comprehensively.We found that the food sensitization rate of children in Jiangxi Province was high,with positive skin prick test rate of 22.15%,positive s Ig E rate of 27.80%,probable food allergy rate of 4.70%,and confirmed food allergy rate of 1.95%.The main foods causing allergies are shrimp,crab,eggs and shellfish.With China’s economic growth and adoption of westernized lifestyles,the prevalence of food allergy may increase dramatically.2.Single factor analysis showed that age,family size,feeding practices,smoke exposure,vitamin D levels,and other allergic diseases might be related to the prevalence of food allergy in the pediatric population in Jiangxi Province.Multifactorial logistic regression analysis indicated vitamin D level might influence the risk of food allergy prevalence related to an OR of 1.04.Vitamin D may influence the incidence and prevalence of food allergy through the modulation of immune response and antimicrobial maintenance of flora homeostasis by calcitriol,the major metabolite of vitamin D.3.We selected functional single nucleotide polymorphisms in key genes according to the vitamin D metabolic pathway to analyze the association between polymorphisms in vitamin D signaling pathway genes and food allergy.Genotyping was performed using Mass ARRAY platform.Association analyses showed that the locus encoding vitamin D receptor,rs1544410,was associated with both probable food allergy and confirmed food allergy,with increased susceptibility to food allergy in individuals carrying mutant genotypes;statistically significant associations were detected between rs2248359 in CYP24A1 gene and food sensitization,no significant association was found between other loci and food allergy;The haplotype consisting of 8 polymorphisms loci was found to be associated with food sensitivity,but not food allergy.Mutations in certain loci on the genes encoding key molecules of the vitamin D metabolism pathway may directly or indirectly(e.g.,affecting expression products,cytokines,or levels of vitamin D)affect the immune response to food in individual or population,and thus influence the occurrence and severity of food allergy.4.The levels of vitamin D receptor,vitamin D binding protein and the cytokines: IFN-γ,IL4,IL-6,IL17,IL10 and IL13 in the serum were detected by enzyme-linked immunosorbent assay and flow fluorescence detection,respectively.The associations of single nucleotide polymorphism with vitamin D,vitamin D receptor,vitamin D-binding proteins,and cytokines were analyzed,as well as the correlations between vitamin D and cytokines.The results showed that single nucleotide polymorphism of rs2248359 in CYP24A1 gene was associated with vitamin D levels,and the levels of vitamin D were decreased after the mutation;the single nucleotide polymorphism locus rs2228570 encoding the vitamin D receptor gene was associated with the levels of vitamin D receptor;and the polymorphisms of the three candidate loci of the Vitamin D binding protein gene did not have statistically significant association with the level of Vitamin D binding protein.Vitamin D levels were weakly positively and negatively correlated with cytokines IFN-r and IL-6,respectively;Vitamin D receptor and vitamin D binding protein levels had no significant relationship with food allergy,and their effects on food allergy might be realized through vitamin D.Vitamin D may influence food allergy by influencing the cytokine levels and then affecting food allergic reactions.Further studies on the effect of vitamin D on food allergy and its mechanism are needed.5.Multifactor dimensionality reduction was used to analyze whether there were interactions between genes and genes and between genes and vitamin D and other environmental factors,and whether the results of the interactions would have an effect on the risk of developing food allergy.rs1544410 antagonistically interacted with the candidate locus of the Vitamin D binding protein gene;There were thirdorder interactions among rs2228570,rs2282679 and rs7041,with combination of pure mutant genotype increasing the susceptibility to food allergy;Second-order interaction was found between vitamin D and rs2282679,the locus encoding the vitamin D receptor gene;Interactions between birth season,rs1050084,and vitamin D had influence on food allergy.Early environmental exposures might have an effect on gene expression and food allergy.Children born in winter and carrying purely variant genotypes appeared to be more susceptible to food allergy.The optimal interaction model based on polymorphisms of vitamin D metabolic pathway genes to assess an individual’s risk of food allergy needs to be further validated and studied in clinical practice in order to clarify whether these polymorphisms interact at the biological level.