title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Byung-Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Charisse Flerida A
authors.initials: CF
authors.lastname: Pasaje
authors.forename: Joon Seol
authors.initials: JS
authors.lastname: Bae
authors.forename: Jong Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Soo-Taek
authors.initials: ST
authors.lastname: Uh
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Kim
authors.forename: Inseon S
authors.initials: IS
authors.lastname: Choi
authors.forename: Byoung Whui
authors.initials: BW
authors.lastname: Choi
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D055963:Asthma, Aspirin-Induced / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D003937:Diagnosis, Differential; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D059805:HLA-DR alpha-Chains / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D056910:Republic of Korea; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D059805:HLA-DR alpha-Chains