KIF3A genetic variation is associated with pediatric asthma in the presence of eczema independent of allergic rhinitis.
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ABSTRACT:
SUBMITTER: Johansson E
PROVIDER: S-EPMC5546923 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
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KIF3A genetic variation is associated with pediatric asthma in the presence of eczema independent of allergic rhinitis.
Johansson Elisabet E Biagini Myers Jocelyn M JM Martin Lisa J LJ He Hua H Pilipenko Valentina V Mersha Tesfaye T Weirauch Matthew M Salomonis Nathan N Ryan Patrick P LeMasters Grace K GK Bernstein David I DI Lockey James J Khurana Hershey Gurjit K GK
The Journal of allergy and clinical immunology 20170224 2
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Project description:BackgroundLittle is known about the prevalence of asthma, allergic rhinitis, eczema and allergies among Canadian Inuit children, especially those living in the arctic and subarctic areas.MethodsA cross-sectional study among Grade 1 students attending schools in Iqaluit, the capital of Nunavut, was conducted during the 2015/2016 school year. We used the International Study of Allergy and Asthma in Children questionnaire with added questions relevant to the population. In addition, skin prick tests were conducted to test for sensitization to common food and environmental allergens.ResultsThe prevalence of current asthma was 15.9% (> 2:1 males) with the highest prevalence among those with any non-Inuit heritage at 38.5%. The prevalence of current and past allergic rhinitis was 6.8%, also predominant among males, with the lowest prevalence among the mixed ethnicity. Home crowdedness was inversely related to past asthma. Being ever outside Nunavut was associated with higher prevalence of current and past asthma. No statistically significant relationship was found with passive smoking or exclusive breast feeding during the first 4 months of life. The current eczema prevalence was 20.5%, with the highest prevalence recorded among the Inuit at 25% compared to 15.4% among the mixed ethnicity and 14.3% among the non-Inuit. We noted a high rate of sensitization to cat at 26.7% while absent sensitization to other common inhalant allergens.ConclusionVariations in the prevalence and risk factors of asthma, allergic rhinitis and eczema among different ethnicities living at the same subarctic environment may be related to genetic, gene-environment interaction and/or lifestyle factors that require further investigation.
| S-EPMC5827980 | biostudies-literature
Project description:The occurrence of allergic multimorbidity (coexistence of asthma, allergic rhinitis and eczema) has not been evaluated longitudinally from early childhood up to adulthood in a population-based study sample. We aimed to determine the prevalence of allergic multimorbidity up to age 20 stratified by parental allergies and sex/gender using extensive prospective follow-up data from two decades of a birth cohort study.In 1990, we recruited 1314 healthy newborns from 6 maternity wards across Germany for the population-based MAS birth cohort study. The sample was purposely risk-enriched by increasing the proportion of children at high allergy risk (i.e. at least 2 allergic family members among parents and siblings) from 19% in the source population to 38% in the final sample. The remaining 62% of all MAS children had a low or no allergy risk. Symptoms, medication and doctor's diagnoses of allergic diseases have been assessed using standardized questionnaires including validated ISAAC questions in 19 follow-up assessments up to age 20. Allergic multimorbidity at each time point was defined as the coexistence of at least 2 of the following diseases in one participant: asthma, allergic rhinitis and eczema.Response at age 20 was 72% (n = 942) of all recruited participants. At age 20, 18.5% (95% CI, 15.0-22.5%) of all participants with allergic parents had 2 or 3 concurrent allergies as compared to only 6.3% (95% CI, 4.3-9.0%) of those with non-allergic parents. At this age, allergic multimorbidity was similar in women and men (12.7% (95% CI, 9.7-16.2%) vs. 11.6% (95% CI, 8.9-14.8%)), whereas single allergic diseases were slightly more common in women than men (24.2% (95% CI, 20.2-28.5%) vs. 20.1% (95% CI, 16.6-24.0%)). Asthma occurred more frequently with coexisting allergic rhinitis and/or eczema than as a single entity from pre-puberty to adulthood.Having parents with allergies is not only a strong predictor to develop any allergy, but it strongly increases the risk of developing allergic multimorbidity. In males and females alike, coexisting allergies were increasingly common throughout adolescence up to adulthood. Particularly asthma occurred in both sexes more frequently with coexisting allergies than as a single entity.
| S-EPMC4744942 | biostudies-other
Project description:Associations of variants of the filaggrin gene, i.e. FLG with asthma and rhinitis have been shown to be modulated by eczema status. However, it is unknown whether allergic sensitization status modifies this association. The aim of this study was to determine whether FLG variants need eczema and/or allergic sensitization as a necessary component to execute adverse effects on coexisting and subsequent asthma and rhinitis.In the Isle of Wight birth cohort, repeated measurements of asthma, rhinitis, eczema and allergic sensitization (documented by skin-prick tests) were taken in 1,456 children at the ages of 1, 2, 4, 10 and 18 years. Filaggrin haploinsufficiency was defined as having at least the minor allele of R501X, 2282del4 or S3247X variants. log-binomial regression models were used to test associations and statistical interactions.FLG variants increased the risk of asthma [risk ratio (RR) 1.39, 95% confidence interval (CI) 1.06-1.80] and rhinitis (RR 1.37, 95% CI 1.16-1.63). In the delayed-effects models, 'FLG variants plus allergic sensitization' and 'FLG variants plus eczema' increased the risk of subsequent asthma by 4.93-fold (95% CI 3.61-6.71) and 3.33-fold (95% CI 2.45-4.51), respectively, during the first 18 years of life. In contrast, neither eczema nor allergic sensitization in combination with FLG variants increased the risk of later rhinitis.Allergic sensitization and eczema modulated the association between FLG variants and asthma but not rhinitis. Our results imply that the mechanisms and pathways through which FLG variants predispose to an increased risk of asthma and rhinitis may be different.
| S-EPMC4281035 | biostudies-literature
Project description:BackgroundAllergic diseases (eczema, wheeze and rhinitis) in children often present as heterogeneous phenotypes. Understanding genetic associations of specific patterns of symptoms might facilitate understanding of the underlying biological mechanisms.ObjectiveTo examine associations between allergic disease-related variants identified in a recent genome-wide association study and latent classes of allergic diseases (LCADs) in two population-based birth cohorts.MethodsEight previously defined LCADs between birth and 11 years: "No disease," "Atopic march," "Persistent eczema and wheeze," "Persistent eczema with later-onset rhinitis," "Persistent wheeze with later-onset rhinitis," "Transient wheeze," "Eczema only" and "Rhinitis only" were used as the study outcome. Weighted multinomial logistic regression was used to estimate associations between 135 SNPs (and a polygenic risk score, PRS) and LCADs among 6345 individuals from The Avon Longitudinal Study of Parents and Children (ALSPAC). Heterogeneity across LCADs was assessed before and after Bonferroni correction. Results were replicated in Manchester Asthma and Allergy Study (MAAS) (n = 896) and pooled in a meta-analysis.ResultsWe found strong evidence for differential genetic associations across the LCADs; pooled PRS heterogeneity P-value = 3.3 × 10-14 , excluding "no disease" class. The associations between the PRS and LCADs in MAAS were remarkably similar to ALSPAC. Two SNPs (a protein-truncating variant in FLG and a SNP within an intron of GSDMB) had evidence for differential association (pooled P-values ≤ 0.006). The FLG locus was differentially associated across LCADs that included eczema, with stronger associations for LCADs with comorbid wheeze and rhinitis. The GSDMB locus in contrast was equally associated across LCADs that included wheeze.Conclusions and clinical relevanceWe have shown complex, but distinct patterns of genetic associations with LCADs, suggesting that heterogeneous mechanisms underlie individual disease trajectories. Establishing the combination of allergic diseases with which each genetic variant is associated may inform therapeutic development and/or predictive modelling.
| S-EPMC6899469 | biostudies-literature
Project description: Not available
| S-EPMC9303559 | biostudies-literature
Project description:BackgroundThe mechanisms explaining the co-existence of asthma, eczema and rhinitis (allergic multimorbidity) are largely unknown. We investigated the mechanisms underlying multimorbidity between three main allergic diseases at a molecular level by identifying the proteins and cellular processes that are common to them.MethodsAn in silico study based on computational analysis of the topology of the protein interaction network was performed in order to characterize the molecular mechanisms of multimorbidity of asthma, eczema and rhinitis. As a first step, proteins associated to either disease were identified using data mining approaches, and their overlap was calculated. Secondly, a functional interaction network was built, allowing to identify cellular pathways involved in allergic multimorbidity. Finally, a network-based algorithm generated a ranked list of newly predicted multimorbidity-associated proteins.ResultsAsthma, eczema and rhinitis shared a larger number of associated proteins than expected by chance, and their associated proteins exhibited a significant degree of interconnectedness in the interaction network. There were 15 pathways involved in the multimorbidity of asthma, eczema and rhinitis, including IL4 signaling and GATA3-related pathways. A number of proteins potentially associated to these multimorbidity processes were also obtained.ConclusionsThese results strongly support the existence of an allergic multimorbidity cluster between asthma, eczema and rhinitis, and suggest that type 2 signaling pathways represent a relevant multimorbidity mechanism of allergic diseases. Furthermore, we identified new candidates contributing to multimorbidity that may assist in identifying new targets for multimorbid allergic diseases.
| S-EPMC5466323 | biostudies-literature
Project description:Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.
| S-EPMC5989923 | biostudies-literature
Project description:Aims/hypothesisThis paper presents the relationship between islet autoantibodies, precursors of type 1 diabetes, and the development of persistent asthma, allergic rhinitis and atopic eczema.MethodsA total of 2159 newborns who had a first-degree relative with type 1 diabetes and selected HLA genotypes were followed until the youngest participant reached 10 years of age. Islet cell antibodies (ICA) were detected using indirect immunofluorescence. Autoantibodies to insulin (IAA), GAD (GADA), the tyrosine phosphatase-related insulinoma-associated 2 molecule (IA-2A) and zinc transporter 8 (ZnT8A) were quantified with the use of specific radiobinding assays. As an ancillary study, the incidence of asthma, allergic rhinitis and eczema was assessed in 1106 of these children using the International Study of Asthma and Allergies in Childhood (ISAAC) core questionnaire when the children were 9-11 years old. HRs with 95% CIs were calculated to depict the incidence of these diseases following seroconversion to autoantibody positivity.ResultsThe cumulative incidence of atopic eczema, allergic rhinitis and persistent asthma were 22%, 9% and 7.5%, respectively, by 9-11 years of age. The occurrence of diabetes-related autoantibodies showed a protective association with subsequently reported incidence of asthma and eczema. The incidence of rhinitis was not significantly related to the occurrence of IAA or GADA (statistical power was limited), but demonstrated the same inverse relationship as did the other diseases with ICA or when multiple autoantibodies first appeared together.Conclusions/interpretationThe findings add evidence to the relationships between these atopic diseases and diabetes-related autoimmunity and also suggest that, for eczema, the interaction depends upon which autoantibody appeared first.Trial registrationClinicalTrials.gov NCT00179777 Graphical abstract.
| S-EPMC7416479 | biostudies-literature
Project description:BackgroundThe rates of childhood allergic conditions are changing, prompting the need for continued surveillance. Examination of healthcare provider-based diagnosis data is an important and lacking methodology needed to complement existing studies that rely on participant reporting.MethodsUtilizing our care network of 1,050,061 urban and sub-urban children, we defined two retrospective cohorts: (1) a closed birth cohort of 29,662 children and (2) a cross-sectional cohort of 333,200 children. These cohorts were utilized to determine the epidemiologic characteristics of the conditions studied. Logistic regression was utilized to determine the extent to which food allergy was associated with respiratory allergy.ResultsIn our birth cohort, the peak age at diagnosis of eczema, asthma, rhinitis, and food allergy was between 0 and 5 months (7.3 %), 12 and 17 months (8.7 %), 24 and 29 months (2.5 %), and 12 and 17 months (1.9 %), respectively. In our cross-sectional cohort, eczema and rhinitis prevalence rates were 6.7 % and 19.9 %, respectively. Asthma prevalence was 21.8 %, a rate higher than previously reported. Food allergy prevalence was 6.7 %, with the most common allergenic foods being peanut (2.6 %), milk (2.2 %), egg (1.8 %), shellfish (1.5 %), and soy (0.7 %). Food allergy was associated with development of asthma (OR 2.16, 95 % CI 1.94-2.40), and rhinitis (OR 2.72, 95 % CI 2.45-3.03).ConclusionsCompared with previous reports, we measure lower rates of eczema and higher rates of asthma. The distribution of the major allergenic foods diverged from prior figures, and food allergy was associated with the development of respiratory allergy. The utilization of provider-based diagnosis data contributes an important and lacking methodology that complements existing studies.
| S-EPMC4992234 | biostudies-literature
Project description:BACKGROUND:Allergic sensitization is associated with eczema, asthma, and rhinitis. However, it is unknown whether and how allergic sensitization is associated over time with acquisition, remission, and persistence of these diseases and their comorbidity. OBJECTIVE:To gain a better understanding of factors including allergic sensitization transitions that influence the temporal pattern of asthma, eczema, and rhinitis and their comorbidity during childhood. METHODS:In the Isle of Wight birth cohort, information on allergic sensitization to common allergens was collected at ages 4, 10, and 18 years along with asthma, rhinitis, and eczema status determined by clinical diagnosis. Logistic regressions were used to estimate subsequent and concurrent odds ratios of diseases transition with allergic sensitization transition status as the main independent variable. Two transition periods were considered, 4 to 10 years of age and 10 to 18 years of age. RESULTS:The odds of new diagnosis of allergic disease (no-yes) was increased among subjects with acquired or persistent allergic sensitization to common allergens compared to subjects with no sensitization (acquisition of sensitization odds ratio [OR]=3.22, P < .0001; persistence of sensitization, OR=6.33, P < .0001). The odds of remission of allergic diseases (yes-no) was lower among subjects with acquired or sustained allergic sensitization (acquisition, OR=0.18, P = .0001; persistence, OR=0.085, P < .0001), compared to subjects not sensitized. Subjects with acquired or persistent allergic sensitization were also had higher odds for persistence of disease (yes-yes) than subjects not sensitized (acquisition, OR=5.49, P = .0001; persistence, OR=11.79, P < .0001). CONCLUSION:Transition of allergic sensitizations to common allergens is a prognostic factor for subsequent or concurrent transition of eczema, asthma, and rhinitis. Prevention or reduction in allergic sensitization has a potential to lead to remission of these conditions.
| S-EPMC5924466 | biostudies-literature