title: 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.
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA. Supinda@post.harvard.edu
authors.forename: Supinda
authors.initials: S
authors.lastname: Bunyavanich
authors.forename: Josef
authors.initials: J
authors.lastname: Shargorodsky
authors.forename: Juan C
authors.initials: JC
authors.lastname: Celedón
mesh_terms: D000328:Adult; D000367:Age Factors; D002648:Child; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012221:Rhinitis, Allergic, Perennial / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D006255:Rhinitis, Allergic, Seasonal / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D012306:Risk; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: C504000:IL4R protein, human; D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit