Genetic evidence for CFTR dysfunction in Japanese: background for chronic pancreatitis
Genetic evidence for CFTR dysfunction in Japanese: background for chronic pancreatitis
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DOI：
10.1136/jmg.2003.014456
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发表时间：
2004-05-01
影响因子：
4
通讯作者：
Naruse, S
中科院分区：
文献类型：
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作者：
Fujiki, K;Ishiguro, H;Naruse, S
囊性纤维化跨膜传导调节因子（CFTR）是在许多上皮组织中表达的cAMP调节的Cl 2通道。1在胰腺中，CFTR在导管细胞的顶端HCO 3-转运中起关键作用。2-5由于CFTR基因突变导致其功能丧失，导致胰腺囊性纤维化（CF）伴外分泌功能不全、慢性气道疾病和汗液氯化物浓度异常升高。现在已经鉴定出CFTR中超过1000个突变和200个多态性位点。6这些突变和多态性赋予了从典型CF到非典型CF的相当可变的表型，其具有不太严重的肺部病变、胰腺功能不全和正常或临界汗液氯化物浓度。7 8现在人们已经认识到，CFTR相关疾病的范围比以前认为的要广得多。9有些人可能表现出明显的单一临床特征或单一症状的疾病，如慢性鼻窦炎、先天性双侧输精管缺如（CBAVD）和汗液氯化物异常。最近的证据10 -12表明，慢性胰腺炎，至少在一个子集的病人，属于这组疾病。慢性胰腺炎是一种进行性胰腺炎性疾病，可导致胰腺腺泡细胞丢失、导管异常（常伴导管内结石）和不规则纤维化。酒精是男性慢性胰腺炎最常见的原因，但特发性胰腺炎在女性中更常见。西方国家慢性胰腺炎的发病率（约4/100 000人口）与美国（5.425/100 000人口）相似。9/10万）。14然而，与白人（每2500例活产1例）相比，日本人的CF发病率非常低（每350000例中1例）。CF和慢性胰腺炎发病率的明显差异可能不支持日本人存在CFTR功能障碍。然而，法国16和日本17的早期研究以及我们最近的研究18表明，慢性胰腺炎患者汗液中的氯化物浓度较高，表明法国人和日本人都存在CFTR功能障碍。
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP regulated Cl2 channel that is expressed in many epithelial tissues. 1 In the pancreas CFTR plays a key role in the apical HCO3–transport in duct cells. 2–5 Loss of its function due to mutations in the CFTR gene causes cystic fibrosis (CF) of the pancreas with exocrine insufficiency, chronic airway disease, and abnormally elevated sweat chloride concentration. Over 1000 mutations and 200 polymorphic loci in CFTR have now been identified. 6 These mutations and polymorphisms confer quite variable phenotypes from classic CF to atypical CF with less severe pulmonary lesions, pancreatic sufficiency, and normal or borderline sweat chloride concentration. 7 8 It is now well recognised that the spectrum of CFTR related disease is much broader than previously thought. 9 Some individuals may exhibit an apparently single clinical feature or a monosymptomatic disease, such as chronic sinusitis, congenital bilateral absence of the vas deferens (CBAVD), and sweat chloride abnormalities. Recent evidence10–12 suggests that chronic pancreatitis, in at least a subset of the patients, belongs to this group of disease. 13Chronic pancreatitis is a progressive inflammatory disease of the pancreas that causes the loss of pancreatic acinar cells, ductal abnormalities often with intraductal stones, and irregular fibrosis. Alcohol is the most common cause of chronic pancreatitis in men but idiopathic pancreatitis is more common in women. The incidence of chronic pancreatitis in Western countries (about 4 per 100 000 population) is similar to that (5.425. 9 per 100 000) in Japan. 14 However, the incidence of CF in Japanese is very low (1 per 350 000) compared with whites (1 per 2500 live births). 7 15 The apparent large difference of the incidence of CF and chronic pancreatitis may not support the presence of CFTR dysfunction in Japanese. However, earlier studies in France16 and Japan, 17 and our recent study18 demonstrated that patients with chronic pancreatitis have high sweat chloride concentration, indicating the presence of CFTR dysfunction in both French and Japanese.