Self-Reported Allergic Rhinitis and/or Allergic Conjunctivitis Associate with IL13 rs20541 Polymorphism in Finnish Adult Asthma Patients.

BACKGROUND: Our aim was to observe factors associated with IL13 rs20541 polymorphism and other factors with or without allergic comorbidities such as subject-reported allergic rhinitis (AR) and/or allergic conjunctivitis (AC) symptoms in adult asthmatics. METHODS: A population-based sample of Finnish adult asthma patients (n = 1,156) and matched controls (n = 1,792) filled in a questionnaire. Asthma was diagnosed based on a typical history of asthma symptoms and lung function tests. Skin prick tests with 17 aeroallergens and blood tests including analysis of interleukin 13 (IL13) rs20541 (G/A) genotypes were performed for a subsample (n = 193). RESULTS: The proportion of asthmatics reporting AR was 61.9% and reporting AC was 40.7%. After adjustments, the presence of the IL13 rs20541A- allele (OR 3.06, 95% CI 1.42-6.58, p = 0.004) or multisensitization (adjusted OR 4.59, 95% CI 1.48-14.26, p = 0.008) was associated with AR/AC asthma. Nasal polyps and acetylsalicylic acid-exacerbated respiratory disease was also associated with AR/AC asthma. CONCLUSIONS: Adult AR/AC asthma could putatively be a phenotype, characterized by the presence of atopic and/or eosinophilic factors and a high prevalence of the IL13 rs20541A- allele. Studies on the mechanisms behind this and in other populations are needed.

Epistatic effect of TLR4 and IL4 genes on the risk of asthma in females.

BACKGROUND: Many studies have demonstrated a connection between asthma and T-cell cytokine genes, such as genes coding for interleukin-4 (IL4) and IL-13, which are involved in the regulation of the TH1/TH2 balance. The toll-like receptor 4 (TLR4), the principal receptor for bacterial endotoxin, has attracted attention as a potential risk factor for asthma. We examined whether the polymorphisms of the TLR4 (A/G at +896) and IL4 (C/T at -590) showed an epistatic effect on the risk of asthma or atopy. METHODS: Gene polymorphism analyses and skin prick tests were performed on asthmatic and nonasthmatic adult subjects of a Finnish population-based case-control study. The phenotype studied was persistent asthma. RESULTS: The results showed that genotypes of neither the TLR4 SNP at +896 nor IL4 SNP at -590 were separately found to be associated with asthma. However, the female carriers of allele G (i.e. genotype AG or GG) of TLR4 and allele T (genotype CT or TT) of IL4 had a significantly increased risk for asthma. No association of these genes and atopy was found. CONCLUSIONS: Our results indicate that in females the TLR4 and IL4 genes show an epistatic effect on the risk of asthma. The low LPS-responsive allele G of TLR4 and high IgE production allele T of IL4 were found to be the predisposing combination. However, there was no epistatic effect on the risk of atopy.

Epistatic effect of IL1A and IL4RA genes on the risk of atopy.

BACKGROUND: Several studies have demonstrated a linkage or association of the atopic phenotype with T-cell cytokine genes involved in the regulation of the TH1/TH2 balance (eg, IL4, IL13, and their common receptor, IL4RA). We have recently shown that polymorphism of the pro-inflammatory cytokine IL1A gene is strongly associated with atopy. OBJECTIVE: We now examined whether the polymorphisms of IL1A (G/T at +4845) and IL4RA (T/C at +22446) would show an epistatic effect on the risk of atopy. METHODS: Skin prick tests and gene polymorphism analyses were performed in a population-based sample of asthmatic and nonasthmatic subjects. RESULTS: Our results showed that in the nonasthmatic group the previously described elevated risk of atopy in noncarriers of allele T of IL1A (ie, having the genotype GG) was restricted to individuals who were also noncarriers of allele C of IL4RA (genotype TT). This finding applies to the general population of Finland, where 3.3% of adults are asthmatic. CONCLUSION: These data suggest that the IL1A and IL4RA genes show an epistatic effect on the risk of atopy.