vuillermin-geneticvariationattheTh2-2017.pdf (107.21 kB)
Genetic variation at the Th2 immune gene IL13 is associated with IgE-mediated paediatric food allergy
journal contribution
posted on 2017-08-01, 00:00 authored by S E Ashley, H-T T Tan, R Peters, K J Allen, Peter VuillerminPeter Vuillermin, S C Dharmage, M L K Tang, J Koplin, A Lowe, A-L Ponsonby, John Desmond Molloy, M C Matheson, R Saffery, J A Ellis, D Martino, HealthNuts teamBACKGROUND: Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells.
OBJECTIVE: Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy.
METHOD: We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed. RESULTS: IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE.
CONCLUSIONS AND CLINICAL RELAVANCE: We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.
OBJECTIVE: Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy.
METHOD: We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed. RESULTS: IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE.
CONCLUSIONS AND CLINICAL RELAVANCE: We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.
History
Journal
Clinical & Experimental AllergyVolume
47Issue
8Pagination
1032 - 1037Publisher
Wiley-Blackwell PublishingLocation
Chichester, Eng.Publisher DOI
Link to full text
ISSN
0954-7894eISSN
1365-2222Language
engPublication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2017, John Wiley & SonsUsage metrics
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Keywords
IL13Immunoglobulin Efood allergyfood sensitizationinterleukin-13single nucleotide polymorphismScience & TechnologyLife Sciences & BiomedicineAllergyImmunologyGERMAN MULTICENTER ATOPYINTERLEUKIN-13 GENECOHORT PROFILEASTHMAPOLYMORPHISMPOPULATIONPEANUTINFLAMMATIONPREVALENCEPREDICTORS\nIL13\nHealthNuts teamImmunology
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