Four-Gene Model Linked with Allergic Disease in Toddlers


New research adds to the case that some children are genetically more susceptible to allergic disease.

New research suggests a four-gene model associated with asthma and atopy in children is also associated with the development of allergic diseases in toddlers.

The study suggests it may be possible to predict which toddlers will go on to have allergic disease. The findings add to growing research into the genetic underpinnings of allergies and related conditions.

Investigators including co-corresponding author Yixiao Bao, MD, PhD, of Shanghai Jiao Tong University School of Medicine, in China, had previously developed a 4-gene model showing that a genetic interaction between IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 could be used to determine asthma susceptibility in Han Chinese children using multifactor-dimensionality reduction.

Having confirmed the association between the four-gene model and asthma and atopy in Han Chinese children, the authors set out to determine whether the model was also associated with allergies in early life. To find out, they applied their gene model to a birth cohort of 579 Han Chinese children, with a two-year follow-up period.

The investigators took epidemiological information and cord blood from participants and then genotyped the enrollees for polymorphisms. The participants were then put into high- or low-risk groups based on their genotypes. Allergic disease information was obtained via questionnaire at 6, 12, and 24 months.

Nearly half (284) of the children were placed into the high-risk category, and the remaining 313 were considered low risk. In terms of subject characteristics, the only significant difference between the high- and low-risk groups was found in delivery mode, with toddlers delivered via caesarean section somewhat more likely to be in the high-risk category.

After stratification for delivery mode, the authors found patients in the high-risk category had a higher rate of eczema after 2 years (relative risk [RR], 1.46; P = .040). However, the authors did not find an association between genetic risk and food allergy, wheezing, and allergic rhinitis.

Bao and colleagues said their findings align with earlier research, noting that allergic diseases have been linked with immunoglobulin E- (IgE) mediated inflammatory reactions.

IL13, IL4, ADRB2, and FCER1B, which constitute the gene model, are all involved in IgE-mediated allergic responses,” they wrote.

The authors suggested that the single-nucleotide polymorphisms (SNPs) they identified “interact with each other via the IgE-mediated inflammatory pathway in the pathogenesis of allergic eczema.”

They said further study into the biological interactions between the SNPs is warranted.

As for the lack of an association between the gene model and food allergy, wheezing, and allergic rhinitis, the investigators suggested it was possible their study design did not allow for the recognition of an association. They said a longer follow-up period or the use of objective measures such as prick tests, rather than parent reports, might be needed to confirm or disprove an association.

The authors cited a number of limitations. They noted that their study was limited to 4 genes. While those genes were chosen based on extensive previous study, it is possible that additional genes are involved, as other studies have suggested. Furthermore, they said genetic risk in this study was calculated based on the number of risk allele homozygotes, and thus the specific roles of single risk alleles was not considered.

The study, “Association of a four‐gene model with allergic diseases: Two‐year follow‐up of a birth cohort study,” was published online in Immunity, Inflammation and Disease.

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