title: Investigating highly replicated asthma genes as candidate genes for allergic rhinitis.
abstract: BACKGROUND
  Asthma 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  Genetic 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.
authors.affiliation: Department of Biological Sciences, National University of Singapore, Science Drive 4, Singapore, 117543, Singapore. anand_andiappan@immunol.a-star.edu.sg
authors.forename: Anand Kumar
authors.initials: AK
authors.lastname: Andiappan
authors.forename: Daniel
authors.initials: D
authors.lastname: Nilsson
authors.forename: Christer
authors.initials: C
authors.lastname: Halldén
authors.forename: Wang De
authors.initials: WD
authors.lastname: Yun
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Säll
authors.forename: Lars Olaf
authors.initials: LO
authors.lastname: Cardell
authors.forename: Chew Fook
authors.initials: CF
authors.lastname: Tim
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D001249:Asthma / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics; D016022:Case-Control Studies; D004261:DNA Replication; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population / Q000379:methods; D015894:Genome, Human; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics; D008297:Male; D010641:Phenotype; D011058:Pollen / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics*; D012621:Seasons; D012846:Singapore / Q000453:epidemiology; D018709:Statistics, Nonparametric
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C578095:IL13 protein, human; D018793:Interleukin-13; C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi