Poor Reproducibility of Allergic Rhinitis SNP Associations

10.1371/journal.pone.0053975PLoS ONE81

Evaluation of the applicability of the Immuno-solid-phase allergen chip (ISAC) assay in atopic patients in Singapore

BACKGROUND/OBJECTIVE: Molecular-based allergy diagnostics are gaining popularity in clinical practice. Our aim was to evaluate their role in the tropics, given the inherent genetic and environmental differences. METHODS: We recruited subjects with history of atopy and collected data on demographics and atopic symptoms using validated questionnaires. Subjects underwent a series of skin prick tests (SPT). Serum total and specific IgE levels were measured using ImmunoCAP FEIA and ImmunoCAP ISAC®, respectively. We describe their pattern of sensitization and agreement between test methods. RESULTS: A total of 135 subjects were recruited; mean ± SD age of 31.18 ± 12.72 years, 52.7% female. Allergic rhinitis (AR) was the most prevalent clinical manifestation of atopy (70.7%), followed by atopic dermatitis (AD) (50.5%) and asthma (26.2%). Polysensitization was seen in 51.1% of subjects by both SPT and ISAC. House dust mites (HDM) were the dominant allergen, with sensitization in 67.8% and 62% of subjects on SPT and ISAC, respectively. A group of subjects with monosensitization to B. tropicalis was identified. HDM sensitization was strongly associated with AR, while AD and asthma were not associated with sensitization to any allergen. Agreement between SPT and ISAC was mostly suboptimal. Greatest agreement was documented for the measurement of HDM sensitization with both methods (κ = 0.64). Sensitization to the bulk of the remaining allergens in the ISAC panel was infrequent. CONCLUSION: Multiplex methods should not be used as a screening tool, especially in a population with lower rates of polysensitization and a dominant sensitizing allergen. There may be a role in adjusting the antigen spectrum in the ISAC panel to regional differences. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13601-015-0053-z) contains supplementary material, which is available to authorized users

Variation in Uteroglobin-Related Protein 1 (UGRP1) gene is associated with Allergic Rhinitis in Singapore Chinese

<p>Abstract</p> <p>Background</p> <p>Uteroglobin-Related Protein 1 (<it>UGRP1</it>) is a secretoglobulin protein which has been suggested to play a role in lung inflammation and allergic diseases. UGRP1 has also been shown to be an important pneumoprotein, with diagnostic potential as a biomarker of lung damage. Previous genetic studies evaluating the association between variations on <it>UGRP1 </it>and allergic phenotypes have yielded mixed results. The aim of this present study was to identify genetic polymorphisms in <it>UGRP1 </it>and investigate if they were associated with asthma and allergic rhinitis in the Singapore Chinese population.</p> <p>Methods</p> <p>Resequencing of the <it>UGRP1 </it>gene was conducted on 40 randomly selected individuals from Singapore of ethnic Chinese origin. The polymorphisms identified were then tagged and genotyped in a population of 1893 Singapore Chinese individuals. Genetic associations were evaluated in this population comparing 795 individuals with allergic rhinitis, 718 with asthma (of which 337 had both asthma and allergic rhinitis) and 717 healthy controls with no history of allergy or allergic diseases.</p> <p>Results</p> <p>By resequencing the <it>UGRP1 </it>gene within our population, we identified 11 novel and 16 known single nucleotide polymorphisms (SNPs). TagSNPs were then genotyped, revealing a significant association between rs7726552 and allergic rhinitis (Odds Ratio: 0.81, 95% Confidence Interval: 0.66-0.98, P = 0.039). This association remained statistically significant when it was analyzed genotypically or when stratified according to haplotypes. When variations on <it>UGRP1 </it>were evaluated against asthma, no association was observed.</p> <p>Conclusion</p> <p>This study documents the association between polymorphisms in <it>UGRP1 </it>and allergic rhinitis, suggesting a potential role in its pathogenesis.</p

Genome-wide association study identifies PERLD1 as asthma candidate gene

10.1186/1471-2350-12-170BMC Medical Genetics12-BMGM

A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci

Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P < 5 × 10-8, including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P = 5.3 × 10 -21); 6p21.33 near HLA-C and MICA (rs9266772, P = 3.2 × 10 -12); 5p13.1 near PTGER4 (rs7720838, P = 8.2 × 10 -11); 2q33.1 in PLCL1 (rs10497813, P = 6.1 × 10-10), 3q28 in LPP (rs9860547, P = 1.2 × 10-9); 20q13.2 in NFATC2 (rs6021270, P = 6.9 × 10-9), 4q27 in ADAD1 (rs17388568, P = 3.9 × 10-8); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P = 4.8 × 10-8). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P = 1.7 × 10-12), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease

Rationale and design of the multiethnic Pharmacogenomics in Childhood Asthma consortium

AIM: International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium. MATERIALS & METHODS: Investigators of each study participating in PiCA provided data on the study characteristics by answering an online questionnaire. RESULTS: A total of 21 studies, including 14,227 children/young persons (58% male), from 12 different countries are currently enrolled in the PiCA consortium. Fifty six percent of the patients are Caucasians. In total, 7619 were inhaled corticosteroid users. Among patients from 13 studies with available data on asthma exacerbations, a third reported exacerbations despite inhaled corticosteroid use. In the future pharmacogenomics studies within the consortium, the pharmacogenomics analyses will be performed separately in each center and the results will be meta-analyzed. CONCLUSION: PiCA is a valuable platform to perform pharmacogenetics studies within a multiethnic pediatric asthma population

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ОБРАЗОВАНИЕ МЕДИЦИНСКОЕМЕДИЦИНСКИЕ УЧЕБНЫЕ ЗАВЕДЕНИЯПРОФЕССИОНАЛЬНЫЕ КОМПЕТЕНЦИИСТУДЕНТЫ МЕДИЦИНСКИХ УЧЕБНЫХ ЗАВЕДЕНИЙКОМПЕТЕНТНОСТНЫЙ ПОДХОДЦЕННОСТНЫЕ ОРИЕНТАЦИИМЕДИКО-ПРОФИЛАКТИЧЕСКОЕ ДЕЛО (СПЕЦИАЛЬНОСТЬ