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A meta-analysis of Th2 pathway genetic variants and risk for allergic rhinitis.

ABSTRACT: There is a significant genetic contribution to allergic rhinitis (AR). Genetic association studies for AR have been performed, but varying results make it challenging to decipher the overall potential effect of specific variants. The Th2 pathway plays an important role in the immunological development of AR. We performed meta-analyses of genetic association studies of variants in Th2 pathway genes and AR. PubMed and Phenopedia were searched by double extraction for original studies on Th2 pathway-related genetic polymorphisms and their associations with AR. A meta-analysis was conducted on each genetic polymorphism with data meeting our predetermined selection criteria. Analyses were performed using both fixed and random effects models, with stratification by age group, ethnicity, and AR definition where appropriate. Heterogeneity and publication bias were assessed. Six independent studies analyzing three candidate polymorphisms and involving a total of 1596 cases and 2892 controls met our inclusion criteria. Overall, the A allele of IL13 single nucleotide polymorphism (SNP) rs20541 was associated with increased odds of AR (estimated OR=1.2; 95% CI 1.1-1.3, p-value 0.004 in fixed effects model, 95% CI 1.0-1.5, p-value 0.056 in random effects model). The A allele of rs20541 was associated with increased odds of AR in mixed age groups using both fixed effects and random effects modeling. IL13 SNP rs1800925 and IL4R SNP 1801275 did not demonstrate overall associations with AR. We conclude that there is evidence for an overall association between IL13 SNP rs20541 and increased risk of AR, especially in mixed-age populations.

SUBMITTER: Bunyavanich S

PROVIDER: S-EPMC3345814 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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A meta-analysis of Th2 pathway genetic variants and risk for allergic rhinitis.

Bunyavanich Supinda S Shargorodsky Josef J Celedón Juan C JC

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 20110210 4

There is a significant genetic contribution to allergic rhinitis (AR). Genetic association studies for AR have been performed, but varying results make it challenging to decipher the overall potential effect of specific variants. The Th2 pathway plays an important role in the immunological development of AR. We performed meta-analyses of genetic association studies of variants in Th2 pathway genes and AR. PubMed and Phenopedia were searched by double extraction for original studies on Th2 pathwa ...[more]

PMID: 21309855

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Project description:BACKGROUND:Allergic 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. OBJECTIVE:To 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. METHODS:Eight 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. RESULTS:We 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 RELEVANCE:We 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.

Project description:IntroductionAllergic rhinitis (AR) is a common allergic disorder that impairs social and physical functioning as well as quality of life. It is characterized by sneezing, rhinorrhea, congestion, and itching which respond suboptimally to drug therapy. Low-level laser therapy (LLLT) has anti-inflammatory and immunosuppressive properties that have shown promise in some studies. We aimed to systematically review LLLT's effectiveness in treating AR and meta-analyze our findings.MethodsA systematic search of PubMed, Scopus, and Web of Science was conducted on November 24, 2023. All studies investigating LLLT on AR were included, and a pre-post meta-analysis of nasal symptoms (rhinorrhea, nasal congestion, nasal itching, and sneezing) in the LLLT-treated arm was conducted. Rhinoconjunctivitis quality of life questionnaire (RQLQ) scores before and after LLLT were also meta-analyzed alongside a pairwise meta-analysis of LLLT with placebo, acupuncture, steroids/antihistamines, and ultraviolet lasers. A random-effects model was used with a conservative pre-post correlation of 0.4 and standardized mean difference (SMD) as the effect size.ResultsSixteen studies were included in this review, and we found that nasal symptoms are alleviated post-LLLT in people with AR (SMD: -1.4, 95 CI: [-2.07 to -1.13], p value <0.001). RQLQ scores were also reduced after LLLT (SMD = -0.72, 95 CI: [-0.94 to -0.50], p value <0.001), and very few adverse events were reported. This meta-analysis, however, had significant publication bias and heterogeneity. When compared to a placebo, LLLT did not significantly improve nasal symptoms (SMD: -0.69, p value = 0.167), which might mean the post-LLLT nasal symptom alleviation is due to a placebo effect. Comparisons to other treatment modalities were too few to deduce anything meaningful, although it does appear that LLLT is less effective than UV lasers.ConclusionLLLT is most likely effective at alleviating nasal symptomology and has a low likelihood of adverse event incidence, yet more high-quality studies with larger sample sizes are needed to compare LLLT to a placebo to ensure its superiority to the placebo effect, as well as non-inferiority clinical trials to compare it to standard treatments.

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A meta-analysis of Th2 pathway genetic variants and risk for allergic rhinitis.

Publications

A meta-analysis of Th2 pathway genetic variants and risk for allergic rhinitis.

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