HLA-DRA polymorphisms associated with risk of nasal polyposis in asthmatic patients.

Abstract

BACKGROUND Nasal polyps, part of the aspirin triad symptoms, are edematous protrusions arising from the mucosa of the nasal sinuses. Although the causative factors and pathogenesis of the polyps are unknown, the significant effect of human leukocyte antigen-DR (HLA-DR) expression in nasal polyps and genetic associations of the major histocompatibility complex class II, DR alpha (HLA-DRA) with immune-mediated diseases have been revealed. METHODS To investigate the associations of HLA-DRA polymorphisms with nasal polyposis in asthmatic patients and in aspirin-hypersensitive subgroups, 22 single nucleotide polymorphisms (SNPs) were genotyped in a total of 467 asthmatic patients including 158 nasal polyp-positive and 309 polyp-negative subjects. RESULTS Statistical analysis showed that four SNPs (p = 0.0005-0.02; Pcorr = 0.009-0.033) and one haplotype (p = 0.002; Pcorr = 0.029) were significantly associated with the presence of nasal polyposis in asthmatic patients. In further analysis, although significant signals disappeared after corrections for multiple testing, two HLA-DRA polymorphisms (rs9268644C>A, rs3129878A>C) were found to be potential markers for nasal polyp development in aspirin-tolerant asthma (p = 0.005 and 0.007, respectively) compared with the aspirin-exacerbated respiratory disease (p > 0.05) subgroup. In silico analysis predicted major "C" allele of rs14004C>A in 5'-untranslated region as a potential binding site for regulatory glucocorticoid receptor. In addition, sequence nearby rs1051336G>A is suspected to be a pyrimidine-rich element that affects mRNA stability. CONCLUSION Despite the need for replication in larger cohorts and/or functional evaluations, our findings suggest that HLA-DRA polymorphisms might contribute to nasal polyposis susceptibility in patients with asthma.

DOI: 10.2500/ajra.2012.26.3692
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@article{Kim2012HLADRAPA, title={HLA-DRA polymorphisms associated with risk of nasal polyposis in asthmatic patients.}, author={Jeong Hyun Kim and Byung Lae Park and Hyun Sub Cheong and Charisse Flerida Arnejo Pasaje and Joon Seol Bae and Jong Sook Park and Soo-taek Uh and Yong-Hoon Kim and Mi-Kyeong Kim and Inseon S. Choi and Byoung Whui Choi and Choon-Sik Park and Hyoung Doo Shin}, journal={American journal of rhinology & allergy}, year={2012}, volume={26 1}, pages={12-7} }