Department of Life Science, Sogang University, Seoul, Republic of Korea.
Am J Rhinol Allergy. 2012 Jan-Feb;26(1):12-7. doi: 10.2500/ajra.2012.26.3692.
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.
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.
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.
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.
鼻息肉是阿司匹林三联征的一部分，是鼻窦黏膜的水肿性突起。尽管鼻息肉的病因和发病机制尚不清楚，但已揭示人类白细胞抗原-DR（HLA-DR）在鼻息肉中的表达以及主要组织相容性复合体 II 类、DRα（HLA-DRA）与免疫介导性疾病的遗传关联具有重要意义。
为了研究 HLA-DRA 多态性与哮喘患者和阿司匹林过敏亚组中鼻息肉的相关性，对 467 例哮喘患者（包括 158 例鼻息肉阳性和 309 例息肉阴性患者）共进行了 22 个单核苷酸多态性（SNP）的基因分型。
统计分析显示，4 个 SNP（p=0.0005-0.02；Pcorr=0.009-0.033）和 1 个单倍型（p=0.002；Pcorr=0.029）与哮喘患者鼻息肉的存在显著相关。进一步分析显示，尽管经过多重检验校正后，显著信号消失，但在阿司匹林耐受型哮喘中，两个 HLA-DRA 多态性（rs9268644C>A、rs3129878A>C）被发现是鼻息肉发展的潜在标志物（p=0.005 和 0.007），与阿司匹林加重性呼吸道疾病（p>0.05）亚组相比。计算机分析预测 5'-非翻译区 rs14004C>A 的主要“C”等位基因可能是调节糖皮质激素受体的潜在结合位点。此外，rs1051336G>A 附近的序列疑似为影响 mRNA 稳定性的嘧啶丰富元件。
尽管需要在更大的队列中进行复制或功能评估，但我们的研究结果表明，HLA-DRA 多态性可能与哮喘患者的鼻息肉易感性有关。
