Investigating highly replicated asthma genes as candidate genes for allergic rhinitis

Abstract

BackgroundAsthma genetics has been extensively studied and many genes have been associated with the development or severity of this disease. In contrast, the genetic basis of allergic rhinitis (AR) has not been evaluated as extensively. It is well known that asthma is closely related with AR since a large proportion of individuals with asthma also present symptoms of AR, and patients with AR have a 5–6 fold increased risk of developing asthma. Thus, the relevance of asthma candidate genes as predisposing factors for AR is worth investigating. The present study was designed to investigate if SNPs in highly replicated asthma genes are associated with the occurrence of AR.MethodsA total of 192 SNPs from 21 asthma candidate genes reported to be associated with asthma in 6 or more unrelated studies were genotyped in a Swedish population with 246 AR patients and 431 controls. Genotypes for 429 SNPs from the same set of genes were also extracted from a Singapore Chinese genome-wide dataset which consisted of 456 AR cases and 486 controls. All SNPs were subsequently analyzed for association with AR and their influence on allergic sensitization to common allergens.ResultsA limited number of potential associations were observed and the overall pattern of P-values corresponds well to the expectations in the absence of an effect. However, in the tests of allele effects in the Chinese population the number of significant P-values exceeds the expectations. The strongest signals were found for SNPs in NPSR1 and CTLA4. In these genes, a total of nine SNPs showed P-values <0.001 with corresponding Q-values <0.05. In the NPSR1 gene some P-values were lower than the Bonferroni correction level. Reanalysis after elimination of all patients with asthmatic symptoms excluded asthma as a confounding factor in our results. Weaker indications were found for IL13 and GSTP1 with respect to sensitization to birch pollen in the Swedish population.ConclusionsGenetic variation in the majority of the highly replicated asthma genes were not associated to AR in our populations which suggest that asthma and AR could have less in common than previously anticipated. However, NPSR1 and CTLA4 can be genetic links between AR and asthma and associations of polymorphisms in NPSR1 with AR have not been reported previously.

A Nonsynonymous FCER1B SNP is Associated with Risk of Developing Allergic Rhinitis and with IgE Levels

“…Allergic rhinitis, like other complex diseases, results from interplay of genetic and environmental risk factors 3 4 5 . The heritability factor has been calculated to be quite high, between 74–82% 1 and 90% 2 , and several genetic variants are known to be associated with allergic rhinitis risk in some populations 3 28 29 .…”

“…Allergic rhinitis is associated to family history of allergy 1 2 , thus suggesting that genetic risk factors may underlie the risk of developing, or the clinical presentation of, allergic rhinitis 3 4 5 . Allergic rhinitis is also associated to elevated serum IgE levels and increased mediator release from activated inflammatory cells.…”

“…Although the search for genetic susceptibility factors related to allergic rhinitis is a promising field, gene variations related to FcεRI as potential risk factors for allergic rhinitis have not been comprehensively analyzed, and the results available are in some cases contradictory 5 13 14 15 16 17 . The genes coding for all FcεRI subunits are polymorphic.…”

Genetic risk factors for the development of allergic disease identified by genome‐wide association

“…Asthma, AR and AD are clinically diagnosed as discrete diseases; however, the interrelationship between these diseases has long been recognised. For example, individuals with AR have a 5–6-fold greater risk of developing asthma [ 17 , 18 ]. Similarly, it is established that there are shared and distinct genetic components to these diseases with correlation estimates at 0.55 for asthma and eczema, at 0.47 for asthma and rhinitis and at 0.62 for eczema and rhinitis [ 19 ].…”

Single Nucleotide Polymorphism of IL4C-590T and IL4RA 175V and Immunological Parameters in Egyptian Asthmatics with Different Clinical Phenotypes

“…In the view of diversity of these genes, we chose IL4C-590T and IL4RA-175V to evaluate different clinical asthma phenotypes (based on symptomatology) among Egyptian children correlating their clinical and genotyping profiles with airway inflammatory biomarkers. IL-4 and IL-4RA are from the most common candidate asthma genes, positively associated with asthma in many independent studies and were thus highly implicated as true susceptibility genes for asthma-related phenotypes [21,22]. In addition, to the best of our knowledge, no previous studies were done to analyze these two SNPs in Egyptian asthmatic children.…”