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A polymorphism in ORMDL3 is associated not only with asthma without rhinitis but also with chronic obstructive pulmonary disease
Žavbi, Mateja ...
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.
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