Falfán-Valencia Ramcés, Pavón-Romero Gandhi F, Camarena Angel, García María de la Luz, Galicia-Negrete Gustavo, Negrete-García María Cristina, Teran Luis Manuel
HLA Laboratory, Department of Immunogenetics and Allergy, Instituto Nacional de Enfermedades Respiratorias, Tlalpan 4502, Sección XVI, Delegación Tlalpan, 14080 México, DF, Mexico.
J Allergy (Cairo). 2012;2012:741313. doi: 10.1155/2012/741313. Epub 2011 Nov 3.
Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17-7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.
阿司匹林加重性呼吸道疾病(AERD)的特征为慢性增生性鼻窦炎、鼻息肉、哮喘和阿司匹林敏感性。产生这些不耐受表现的机制尚未完全明确,目前的研究集中在环氧合酶1(COX-1)抑制、花生四烯酸代谢以及从COX途径到脂氧合酶(LO)途径,从而诱导白三烯(LT)合成增加。该模型的生物学合理性促使人们寻找负责促炎细胞因子合成的基因中的多态性,如IL1B和IL8。我们对AERD、阿司匹林耐受型哮喘(ATA)和健康对照受试者进行了IL8 - 251(rs4073)和IL1B - 511(rs16944)多态性的基因关联研究。通过实时PCR进行等位基因鉴别,我们发现IL1B(rs16944)的GG和GA基因型在AERD、ATA和健康对照受试者之间的关联无统计学意义。有趣的是,与ATA组相比,AA基因型在AERD患者中的频率增加(基因频率 = 0.19对0.07,p = 0.018,比值比2.98,95%可信区间1.17 - 7.82)。这是首次观察到IL1B多态性与AERD有关。因此,未来的研究必须调查白细胞介素 - 1β是否在AERD患者的气道中释放,以及它是否与IL1B基因中的基因多态性有关。