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首页> 外文期刊>American journal of rhinology >Expression of leukotriene C4 synthase and plasminogen activator inhibitor 1 gene promoter polymorphisms in sinusitis.
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Expression of leukotriene C4 synthase and plasminogen activator inhibitor 1 gene promoter polymorphisms in sinusitis.

机译：白三烯C4合酶和纤溶酶原激活物抑制剂1基因启动子在鼻窦炎中的表达。

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BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
机译：背景：研究已经描述了与白三烯合成和重塑有关的基因中的多态性。白三烯C4合酶（LTC4S）是参与调节半胱氨酰白三烯（CysLT）合成的关键末端途径酶。 LTC4S基因启动子区域中的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。启动子区域中4G或5G残基的存在与转录的改变有关。研究了这些多态性在鼻窦炎和息肉患者中的作用。我们对1996年至2004年间在一家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。方法：从患者中收集人口统计学数据和鼻窦组织。患者分为四组：对照组，慢性增生性嗜酸性鼻窦炎（CHES），阿司匹林加重呼吸道疾病（AERD）和慢性炎性鼻窦炎（CIS）。使用标准PCR技术分析DNA的LTC4S和PAI-1启动子多态性。结果：133例患者中有76例女性和57例男性（平均年龄42岁）。对照组为66人，独联体组为16人，CHES组为51人，AERD组为22人。 LTC4S等位基因频率为对照，A = 0.81和C = 0.19; CIS，A = 0.73，C = 0.27; CHES，A = 0.69，C = 0.31; AERD，A = 0.67，C = 0.33。与对照组相比，CHES中的C等位基因更为频繁（p = 0.04）。 PAI-1等位基因频率为对照，5G = 0.55和4G = 0.45; CIS，5G = 0.47和4G = 0.53; CHES，5G = 0.56和4G = 0.44; AERD，5G = 0.54和4G = 0.46。在CIS中观察到PAI-1基因的4G等位基因表达增加;然而，这四组之间的遗传差异在统计学上没有差异（p> 0.05）。结论：似乎有遗传成分有助于鼻窦炎中鼻息肉的形成。尽管LTC4S多态性以前曾与阿司匹林敏感性哮喘有关，但这是第一个证明该多态性与CHES有关且独立于阿司匹林敏感性的证据。

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