End-organ dysfunction in cystic fibrosis - Association with angiotensin I converting enzyme and cytokine gene polymorphisms
End-organ dysfunction in cystic fibrosis - Association with angiotensin I converting enzyme and cytokine gene polymorphisms
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DOI：
10.1164/rccm.200204-364oc
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发表时间：
2003-02-01
影响因子：
24.7
通讯作者：
Hutchinson, IV
中科院分区：
文献类型：
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作者：
Arkwright, PD;Pravica, V;Hutchinson, IV
囊性纤维化（CF）跨膜传导调节基因功能相似突变患者的临床病程是可变的，因此必然与继发性遗传和环境因素有关。我们检验了某些炎症介质和调节基因的多态性通过影响终末器官损伤程度来影响临床结果的假设。通过使用261名CF白人患者存储的DNA，通过扩增难耐突变系统聚合酶链反应研究临床结果与血管紧张素i转换酶（ACE）和细胞因子基因型之间的可能关联，我们发现肝硬化的超声特征在高生成（DD）基因型患者中比低生成（11）ACE基因型患者更常见（优势比[95%置信区间]，3.7[1.2至12]）。此外，显著的肺功能障碍（FEV1 < 50%的年龄）与高产ACE基因型（2.3[1.2至4.5]）和转化生长因子- β(1)基因型（2.6[1.0至6.8]）以及首次感染铜绿假单胞菌的年龄（9.1[1.1至72]）相关。我们得出结论，高产ACE基因型预测CF患者发生门静脉高压症的几率增加；高产ACE和tgf - β(1)基因型是导致这些患者肺功能障碍的次要遗传因素。
The clinical course of patients with cystic fibrosis (CF) with functionally similar mutations in the CF transmembrane conductance regulator gene is variable and must therefore relate to secondary genetic and environmental factors. We examined the hypothesis that polymorphisms of certain inflammatory mediator and regulatory genes affect clinical outcome by influencing the degree of end-organ damage. By studying the possible association between clinical outcome and angiotensin I-converting enzyme (ACE) and cytokine genotypes by amplification refractory mutation system-polymerase chain reaction, using stored DNA from 261 white patients with CF, we found that ultrasound features of cirrhosis occurred more frequently in patients with the high-producer (DD) rather than the low-producer (11) ACE genotype (odds ratio [95% confidence interval], 3.7 [1.2 to 12]). Moreover, significant pulmonary dysfunction (age at which FEV1 < 50%) was associated with the high-producer ACE genotype (2.3 [1.2 to 4.5]) and transforming growth factor-beta(1) genotype (2.6 [1.0 to 6.8]) as well as with age at first colonization with Pseudomonas aeruginosa (9.1 [1.1 to 72]). We conclude that the high-producer ACE genotype predicts patients with CF who have an increased chance of developing portal hypertension; and high-producer ACE and TGF-beta(1) genotypes are secondary genetic factors contributing to pulmonary dysfunction in these patients.