Genetic determinants of paediatric food allergy: A systematic review

Abstract

Background The genetic determinants of food allergy have not been systematically reviewed. We therefore systematically reviewed the literature on the genetic basis of food allergy, identifying areas for further investigation. Methods We searched three electronic databases (MEDLINE, EMBASE and PubMed) on 9 January 2018. Two authors screened retrieved articles for review according to inclusion criteria and extracted relevant information on study characteristics and measures of association. Eligible studies included those that reported an unaffected nonatopic control group, had genetic information and were carried out in children. Results Of the 2088 studies retrieved, 32 met our inclusion criteria. Five were genome‐wide association studies, and the remaining were candidate gene studies. Twenty‐two of the studies were carried out in a predominantly Caucasian population with the remaining 10 from Asian‐specific populations or unspecified ethnicity. We found FLG, HLA, IL10, IL13, as well as some evidence for other variants (SPINK5, SERPINB and C11orf30) that are associated with food allergy. Conclusions Little genetic research has been carried out in food allergy, with FLG, HLA and IL13 being the most reproducible genes for an association with food allergy. Despite promising results, existing genetic studies on food allergy are inundated with issues such as inadequate sample size and absence of multiple testing correction. Few included replication analyses or population stratification measures. Studies addressing these limitations along with functional studies are therefore needed to unravel the mechanisms of action of the identified genes.

Recent developments and highlights in food allergy

“…Consequently, epithelial dysregulation and mutations or polymorphisms of genes important for skin barrier, such as filaggrin, SPINK5, 1 and SERPINB7, have been linked to eczema development and also food allergy. [2][3][4][5][6] Recently, electrical impedance spectroscopy has shown promising results in rodents to measure skin barrier function. This is of relevance since it can be easily adapted for usage on humans.…”

The Role of Diet Diversity and Diet Indices on Allergy Outcomes

“…In many of these studies, infants were sensitized just before introducing the allergenic food/s (4,24,26,27). This suggests that other factors, including genetics, epigenetics, and gut flora, could take part in FA development before weaning (52)(53)(54)(55)(56).…”

Recent developments and highlights in allergic rhinitis

“…Kurakula et al found that the SNP rs4851765 in FHL2 shows an association with the severity of bronchial hyper‐responsiveness, identifying FHL2 as a novel gene associated with asthma severity in humans. Furthermore, genome‐wide association studies (GWAS) were used to discover susceptibility genes for allergic diseases employing common SNPs, finding novel loci and confirmed the role of some previously described genes . Several loci have been found using GWASs in the last decade, such as HLA, MRPL4, BCAP, C11orf30/LRRC32, and FERD3L, which could be involved in inflammatory system or epithelial barrier functions .…”

“…Furthermore, genome-wide association studies (GWAS) were used to discover susceptibility genes for allergic diseases employing common SNPs, finding novel loci and confirmed the role of some previously described genes. 16,17 Several loci have been found using GWASs in the last decade, such as HLA, MRPL4, BCAP, C11orf30/LRRC32, and FERD3L, which could be involved in inflammatory system or epithelial barrier functions. 18 Wagge et al 19 conducted a GWAS on sensitization to inhalant allergens, suggesting that AR and allergic sensitization might share biologic mechanisms and that allergic sensitization loci generally affect systemic allergic sensitization.…”