TGF-β1 genotype and accelerated decline in lung function of patients with cystic fibrosis
TGF-β1 genotype and accelerated decline in lung function of patients with cystic fibrosis
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DOI：
10.1136/thorax.55.6.459
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发表时间：
2000-06-01
期刊：
影响因子：
10
通讯作者：
Hutchinson, IV
中科院分区：
文献类型：
--
作者：
Arkwright, PD;Laurie, S;Hutchinson, IV
背景-转化生长因子-β（1）的多态性与细胞因子水平的变化有关，与许多组织的纤维化有关。然而，这种细胞因子对囊性纤维化患者器官纤维化的贡献目前尚不清楚。本研究旨在检测TGF-β（1）基因多态性与囊性纤维化患者肺功能障碍发生之间的关系。使用储存在171名白人患者中的DNA进行PCR，这些患者是囊性纤维化跨膜传导调节因子Δ F508突变的纯合子（CFTR）基因。从病历中获得患者的临床信息。结果：与TGF-β 1低生产基因型相比，TGF-β 1高生产基因型10号密码子囊性纤维化患者的肺功能恶化更快。高生产者基因型患者1秒用力呼气量（FEV 1）加速下降至50%预测值和用力肺活量（FVC）加速下降至70%预测值的相对风险为1.74（95% CI 1.11 - 2.73）与1.95相比（95%CI 1.24至3.06）对于具有低生产者基因型的那些。在囊性纤维化患者中，基因型可能在介导肺功能障碍中起作用。需要进一步的研究来确定抑制这些患者的TGF-β 1活性是否可以减缓疾病的进展。
Background-Polymorphisms in transforming growth factor (TGF)-beta(1) associated with variations in cytokine levels are Linked to fibrosis in a number of tissues. However, the contribution of this cytokine to organ fibrosis in patients with cystic fibrosis is presently unclear. This study was undertaken to examine the association between TGF-beta(1) gene polymorphisms and the development of pulmonary dysfunction in patients with cystic fibrosis.Methods-Polymorphisms in the TGF-beta(1) gene defining amino acids of codons 10 and 25 were determined by ARMS-PCR using DNA stored on 171 Caucasian patients who were homozygous for the Delta F508 mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Clinical information on the patients was obtained from medical records.Results-Patients with cystic fibrosis of a TGF-beta(1) high producer genotype for codon 10 had more rapid deterioration in lung function than those with a TGF-beta(1) low producer genotype. The relative risk of accelerated decline in forced expiratory volume in one second (FEV1) to 50% predicted and forced vital capacity (FVC) to 70% predicted of patients with a high producer genotype was 1.74 (95% CI 1.11 to 2.73) compared with 1.95 (95% CI 1.24 to 3.06) for those with a low producer genotype.Discussion-TGF-beta(1) genotppes may have a role in mediating pulmonary dysfunction in patients with cystic fibrosis. Further work is required to determine whether inhibition of TGF-beta(1) activity in these patients may slow disease progression.