ORCID Profile
0000-0002-6935-0418
Current Organisation
Royal College of Physicians of Ireland
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Publisher: Wiley
Date: 04-04-2017
DOI: 10.1111/ALL.13143
Abstract: A defective skin barrier is hypothesized to be an important route of sensitization to dietary antigens and may lead to food allergy in some children. Missense mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions. To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy. We genotyped 71 "tag" single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery s le) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these in iduals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent s le group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components. SPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery s le (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also. We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.
Publisher: Wiley
Date: 23-02-2017
DOI: 10.1111/ALL.13122
Abstract: Ecological evidence suggests vitamin D insufficiency (VDI) due to lower ambient ultraviolet radiation (UVR) exposure may be a risk factor for IgE-mediated food allergy. However, there are no studies relating directly measured VDI during early infancy to subsequent challenge-proven food allergy. To prospectively investigate the association between VDI during infancy and challenge-proven food allergy at 1 year. In a birth cohort (n = 1074), we used a case-cohort design to compare 25-hydroxyvitamin D Within the random subcohort, VDI was present in 45% (105/233) of newborns and 24% (55/227) of infants at 6 months. Food allergy prevalence at 1 year was 7.7% (61/786), and 6.5% (53/808) were egg-allergic. There was no evidence of an association between VDI at either birth (aRR 1.25, 95% CI 0.70-2.22) or 6 months (aRR 0.93, 95% CI 0.41-2.14) and food allergy at 1 year. There was no evidence that VDI during the first 6 months of infancy is a risk factor for food allergy at 1 year of age. These findings primarily relate to egg allergy, and larger studies are required.
Publisher: Springer Science and Business Media LLC
Date: 24-03-2020
DOI: 10.1038/S41467-020-14552-1
Abstract: In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella , a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort ( n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal s les shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri . Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri .
Publisher: Wiley
Date: 24-10-2020
DOI: 10.1111/PAI.13128
Abstract: High folate status in pregnancy has been implicated in the increased prevalence of allergic disease, but there are no published data relating directly measured folate status in pregnancy to challenge-proven food allergy among offspring. The study aim was to examine the association between red blood cell (RBC) folate status in trimester three of pregnancy and allergic disease among offspring. Red blood cell folate levels were measured at 28-32 weeks' gestation in a prospective birth cohort (n = 1074). Food allergy outcomes were assessed in 1-year-old infants by skin prick testing and subsequent food challenge. Eczema was assessed by questionnaire and clinical review. High trimester three RBC folate was defined as greater than (>) 1360 nmol/L. Binomial regression was used to examine associations between trimester three RBC folate and allergic outcomes, adjusting for potential confounders. Red blood cell folate levels were measured in 88% (894/1064) of pregnant women. The mean concentration was 1695.6 nmol/L (standard deviation 415.4) with 82% (731/894) >1360 nmol/L. There was no evidence of either linear or non-linear relationships between trimester three RBC folate and allergic outcomes, nor evidence of associations between high RBC folate and food allergy (adjusted risk ratio (aRR) 2.89, 95% CI 0.90-9.35), food sensitization (aRR 1.72, 95% CI 0.85-3.49), or eczema (aRR 0.97, 95% CI 0.67-1.38). The majority of pregnant women in this study had high RBC folate levels. There was no evidence of associations between trimester three RBC folate and food allergy, food sensitization, or eczema among the offspring, although larger studies are required.
No related grants have been discovered for John Molloy.