ABSTRACT
BACKGROUND: Asthma is a heterogeneous disease, and asthmatic patients without rhinitis more commonly have fixed airway obstruction, a feature that is also typical of chronic obstructive pulmonary disease (COPD). The Dutch hypothesis suggests that both COPD and asthma have common genetic risk factors. The purpose of this study was to assess the association between the polymorphism rs4795405 in the known asthma candidate gene ORMDL3 and asthma with and without rhinitis. We also analyzed COPD in order to investigate whether, in addition to a clinical overlap, there might also be a genetic overlap between COPD and asthma. METHODS: The population of this genetic association study comprised 493 Slovenian adults, distributed as follows: 131 patients with asthma (59 had asthma with rhinitis and 72 asthma without rhinitis), 59 patients with rhinitis only, 133 patients with COPD, and 170 controls. Genotypes for rs4795405 were determined using the TaqMan genotyping assay. RESULTS: rs4795405 was specifically associated with asthma without rhinitis. Assuming a recessive genetic model, we found the CC genotype in 26% of healthy controls, in 24% of patients with asthma with rhinitis (P = .862), and in 44% of patients with asthma without rhinitis (P = .006). Polymorphism rs4795405 was also associated with COPD, for which the CC genotype was found in 37% of cases (P = .045). CONCLUSIONS: rs4795405 was strongly associated with asthma without rhinitis, a subtype of asthma for which a higher degree of airway obstruction was found. These results show the importance of analyzing different asthma phenotypes in genetic association studies. We also observed a genetic overlap between COPD and asthma without rhinitis.
Subject(s)
Airway Obstruction/genetics , Asthma/genetics , Genetic Predisposition to Disease , Membrane Proteins/genetics , Polymorphism, Genetic , Pulmonary Disease, Chronic Obstructive/genetics , Adult , Aged , Airway Obstruction/pathology , Asthma/pathology , Case-Control Studies , Female , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/pathology , Rhinitis/genetics , Rhinitis/pathology , SloveniaABSTRACT
Asthma is one of the most common chronic diseases in childhood. It is well known that genetic variability contributes to asthma risk. One of the most replicated asthma candidate genes is ORM1-like 3 (Saccharomyces cerevisiae) (ORMDL3), which has been associated with childhood asthma susceptibility. Another asthma candidate gene is signal transducer and activator of transcription 6 (STAT6), a regulator of IgE class switching. Gene coding thromboxane A2 receptor (TBXA2R), involved in chronic airway inflammation, has been associated with asthma in several genetic studies. We have studied the association of polymorphism rs4795405 in ORMDL3, rs324011 in STAT6 as well as rs8113232 and rs3786989 in TBXA2R with asthma risk, various asthma phenotypes and asthma-related symptoms. The study group consisted of 154 children with asthma, in whom clinical parameters were measured and whose asthma control and atopic status were determined. A control group comprised 71 healthy children. Genotyping was performed using an allelic discrimination assay. The ORMDL3 polymorphism rs4795405 was suggestively associated with asthma risk. Furthermore, it was significantly associated with nonatopic asthma and asthma without rhinitis. No association was detected between the STAT6 polymorphism rs324011 or the TBXA2R polymorphisms rs8113232 and rs3786989 and asthma susceptibility. However, an association between rs324011 in STAT6 with recurrent wheezing in early childhood and a suggestive association between rs8113232 in TBXA2R with rhinitis in children with asthma were observed. Our results confirmed ORMDL3 as a candidate gene for childhood asthma susceptibility. STAT6 and TBXA2R polymorphisms were not associated with asthma risk, but they were associated with asthma-related symptoms.
