Genetic association analysis of CIITA variations with nasal polyp pathogenesis in asthmatic patients

Bae,Joon  Seol; Pasaje,Charisse   Flerida A.; Park,Byung   Lae; Cheong,Hyun  Sub; Kim,Jeong-Hyun; Uh,Soo-Taek; Park,Choon-Sik; Shin,Hyoung   Doo

doi:10.3892/mmr.2012.1251

Genetic association analysis of CIITA variations with nasal polyp pathogenesis in asthmatic patients

Authors:
- Joon Seol Bae
- Charisse Flerida A. Pasaje
- Byung Lae Park
- Hyun Sub Cheong
- Jeong-Hyun Kim
- Soo-Taek Uh
- Choon-Sik Park
- Hyoung Doo Shin
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Affiliations: Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul 153-803, Republic of Korea, Department of Life Science, Sogang University, Seoul 121-742, Republic of Korea, Division of Allergy and Respiratory Medicine, Soonchunhyang University Seoul Hospital, Seoul 140-743, Republic of Korea, Genome Research Center for Allergy and Respiratory Diseases, Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 420-767, Republic of Korea
Published online on: December 27, 2012 https://doi.org/10.3892/mmr.2012.1251
Pages: 927-934

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Abstract

Nasal polyps are abnormal lesions arising mainly from the nasal mucosa and paranasal sinuses. Since the human class II, major histocompatibility complex, transactivator (CIITA) is a positive regulator of class II, major histocompatibility complex gene transcription, the CIITA gene is thought to be involved in the presence of nasal polyps in asthma and aspirin hypersensitive patients. To investigate the association between CIITA and nasal polyposis, 18 single nucleotide polymorphisms (SNPs) were genotyped in 467 asthmatics who were classified into 158 aspirin-exacerbated respiratory disease (AERD) and 309 aspirin-tolerant asthma (ATA) subgroups. Differences in the frequency distribution of CIITA variations between polyp-positive cases and polyp-negative controls were determined using logistic analyses. Initially, a total of 9 CIITA variants were significantly associated with the presence of nasal polyps in the overall asthma, AERD and ATA groups [P=0.001-0.05, odds ratio (OR)=0.53-2.35 in the overall asthma group; P=0.01-0.02, OR=2.45-2.66 in the AERD group; P=0.001‑0.05, OR=0.45-2.61 in the ATA group using various modes of genetic inheritance]. One the variations (rs12932187) retained this association after multiple testing corrections (Pcorr=0.01) in the overall asthma group. In addition, two variations (rs12932187 and rs11074938) were associated with the presence of nasal polyps following multiple testing corrections (Pcorr=0.02 and 0.04, respectively) in the ATA group. These novel findings suggest that rs12932187 and rs11074938 may constitute susceptibility markers of inflammation of the nasal passages in asthma patients.

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