CFTR AND CHRONIC RHINOSINUSITIS

在美国，慢性鼻窦炎影响大约15%的成年人口。这很可能是多种异常引起的。慢性鼻窦炎是常染色体隐性遗传性囊性纤维化(CF)的一个几乎不变的特征，它是由CFTR基因突变引起的。我们一直在探索鼻窦炎患者CFTR基因缺陷率高于正常人群的可能性。在之前的赠款期间进行的研究发现，慢性鼻-鼻窦炎患者中CF突变携带者的频率增加(n=11)。过多的基因分析和体内评估CFTR功能的研究(汗液氯化物试验和鼻部电位差测量)在没有患者身上得到补充，也没有患者有CF的证据。这些数据表明CFTR在无囊性纤维化的慢性鼻-鼻窦炎中起病因学作用。目前提案的总体目标是通过追求以下目标来探讨CFTR与慢性鼻-鼻窦炎的关系：1.通过对至少100名额外的鼻窦炎患者和临床核心中心登记的另外120名对照进行基因筛查，确定慢性鼻窦炎患者中CF携带者的患病率。2.确定有CF突变的慢性鼻-鼻窦炎患者是否具有区别于无突变的患者的临床和/或生化特征。3.确定具有CF突变的家族成员患慢性鼻窦炎的频率是否高于未遗传CF突变的家族成员。4.确定慢性鼻窦炎在CF基因突变的专性携带者(即囊性纤维化患者的父母)中的患病率是否高于普通人群。使用互补的方法和足够大的人群应该最大限度地减少错误地接受或拒绝慢性鼻-鼻窦炎患者CF突变频率增加的假设的机会。这一点至关重要，因为这一假设的潜在健康影响可能是巨大的，如果正确，可能有助于确定哪些患者可以从目前未用于治疗鼻窦炎的疗法中受益。

Chronic rhinosinusitis affects about 15% of the adult population in the United States. It is likely that a variety of abnormalities give rise to this disorder. Chronic rhinosinusitis is an almost invariable feature of the autosomal recessive disorder Cystic Fibrosis (CF), which is caused by mutations in the CFTR gene. We have been exploring the possibility that patients with rhinosinusitis have a higher rate of defects in the CFTR gene than the normal population. Studies performed during the prior grant period identified an increased frequency of carriers of CF mutations among patients with chronic rhinosinusitis (n=11). Excessive genetic analysis and studies that evaluated CFTR function in vivo (sweat chloride test and nasal potential difference measurement) has been complemented on none patients, and none have evidence of CF. These data suggest that CFTR plays an etiologic role in chronic rhinosinusitis in the absence of cystic fibrosis. The overall goal of the current proposal is to explore the relationship between CFTR and chronic rhinosinusitis by pursuing the following aims: 1. To establish the prevalence of CF carriers among patients with chronic rhinosinusitis by genetically screening at least 100 additional rhinosinusitis patients and an additional 120 controls enrolled by the Clinical Core. 2. To determine whether chronic rhinosinusitis patients with a CF mutation have clinical and/or biochemical features that distinguish them from patients without CF mutations. 3. To determine whether family members that have inherited a CF mutation have a higher frequency of chronic rhinosinusitis than those that have not inherited a CF mutation. 4. To determine whether the prevalence of chronic rhinosinusitis in obligate carriers of CF mutations (i.e. parents of Cystic Fibrosis patients) is higher than in the general population. Use of complementary approaches and sufficiently large populations should minimize the chance of erroneously accepting or rejecting the hypothesis that chronic rhinosinusitis patients have an increased frequency of CF mutations. This is critical since the potential health impact of this hypothesis could be substantial, and if correct, may enable the identification of patients who could benefit from therapies that are not currently employed in the treatment of rhinosinusitis.