de Alarcón Alessandro, Steinke John W, Caughey Robert, Barekzi Elizabeth, Hise Kathleen, Gross Charles W, Han Joseph K, Borish Larry
Department of Otolaryngology Head and Neck Surgery, University of Virginia Health Sciences System, Charlottesville, Virginia 22908, USA.
Am J Rhinol. 2006 Sep-Oct;20(5):545-9. doi: 10.2500/ajr.2006.20.2934.
Studies have described polymorphisms in genes involved with both leukotriene synthesis and remodeling. Leukotriene C4 synthase (LTC4S) is the critical terminal pathway enzyme involved in regulation of cysteinyl leukotriene (CysLT) synthesis. An A-to-C base exchange in the promoter region of the LTC4S gene influences its expression. The plasminogen activator inhibitor (PAI) 1 gene is associated with tissue fibrosis. The presence of either 4G or 5G residues in the promoter region has been associated with altered transcription. The role of these polymorphisms was investigated in patients with sinusitis and polyps. We performed a prospective study of patients undergoing endoscopic sinus surgery at a university hospital between 1996 and 2004.
Demographic data and sinus tissue were collected from patients. Patients were classified into four groups: controls, chronic hyperplastic eosinophilic sinusitis (CHES), aspirin exacerbated respiratory disease (AERD), and chronic inflammatory sinusitis (CIS). DNA was analyzed for the LTC4S and the PAI-1 promoter polymorphisms using standard PCR techniques.
There were 133 patients with 76 women and 57 men (mean age, 42 years). Sixty-six people were in the control group, 16 people were in the CIS group, 51 people were in the CHES group, and 22 people were in the AERD group. The LTC4S allelic frequencies were controls, A = 0.81 and C = 0.19; CIS, A = 0.73 and C = 0.27; CHES, A = 0.69 and C = 0.31; AERD, A = 0.67 and C = 0.33. The C allele was more frequent in CHES versus controls (p = 0.04). The PAI-1 allele frequencies were controls, 5G = 0.55 and 4G = 0.45; CIS, 5G = 0.47 and 4G = 0.53; CHES, 5G = 0.56 and 4G = 0.44; AERD, 5G = 0.54 and 4G = 0.46. Increased expression of the 4G allele of the PAI-1 gene was observed in CIS; however, this genetic variance between the four groups was not statistically different (p > 0.05).
There appears to be a genetic component that contributes to nasal polyp formation in sinusitis. Although the LTC4S polymorphism has previously been associated with aspirin-sensitive asthma, this is the first demonstration that the polymorphism is associated with CHES and this is independent of aspirin sensitivity.
研究已描述了与白三烯合成及重塑相关基因的多态性。白三烯C4合成酶（LTC4S）是参与调节半胱氨酰白三烯（CysLT）合成的关键终末途径酶。LTC4S基因启动子区域的A到C碱基交换会影响其表达。纤溶酶原激活物抑制剂（PAI）1基因与组织纤维化相关。启动子区域存在4G或5G残基与转录改变有关。在鼻窦炎和鼻息肉患者中研究了这些多态性的作用。我们对1996年至2004年间在一所大学医院接受内镜鼻窦手术的患者进行了一项前瞻性研究。
收集患者的人口统计学数据和鼻窦组织。患者被分为四组：对照组、慢性增生性嗜酸性鼻窦炎（CHES）、阿司匹林加重的呼吸系统疾病（AERD）和慢性炎症性鼻窦炎（CIS）。使用标准PCR技术分析DNA的LTC4S和PAI - 1启动子多态性。
共有133例患者，其中76例女性和57例男性（平均年龄42岁）。对照组66人，CIS组16人，CHES组51人，AERD组22人。LTC4S等位基因频率分别为：对照组，A = 0.81，C = 0.19；CIS组，A = 0.73，C = 0.27；CHES组，A = 0.69，C = 0.31；AERD组，A = 0.67，C = 0.33。与对照组相比，CHES组中C等位基因更常见（p = 0.04）。PAI - 1等位基因频率分别为：对照组，5G = 0.55，4G = 0.45；CIS组，5G = 0.47，4G = 0.53；CHES组，5G = 0.56，4G = 0.44；AERD组，5G = 0.54，4G = 0.46。在CIS组中观察到PAI - 1基因4G等位基因表达增加；然而，四组之间的这种基因差异无统计学意义（p>0.05）。
鼻窦炎中似乎存在导致鼻息肉形成的遗传因素。虽然LTC4S多态性先前已与阿司匹林敏感性哮喘相关，但这是首次证明该多态性与CHES相关且独立于阿司匹林敏感性。
