Genetic characterization of a Chinese family with familial idiopathic pulmonary fibrosis

作     者：ZHANG Xin JIANG Jun CHEN Wei-jun SU Long-xiang XIE Li-xin 

作者机构：Department of Respiratory MedicineHainan Branch of Chinese People's Liberation Army General HospitalSanyaHainan 572000China Department of Respiratory MedicineChinese People's Liberation Army General HospitalBeijing 100853China Beijing Institute of GcnomicsChinese Academy of SciencesBeijing 100101China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2012年第125卷第11期

页      面：1945-1951页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：idiopathic pulmonary fibrosis familial interstitial lung disease genetics Chinese 

摘      要：Background Idiopathic pulmonary fibrosis （IPF） is a chronic inflammatory interstitial lung disease with an unknown cause. Recent studies have shown that genetic factors play an important role in the pathogenesis of IPF. Methods To explore the genetic background of patients with IPF, a candidate gene approach was employed to screen for mutations in seven genes among members with familial IPF in mainland of China. Results Within six of the candidate genes, a total of 31 point mutations were identified. Among the missense mutations, the SFTPA1 exon 6 CAG〉AAG （GIn238Lys） and SFTPB exon 2 CAC〉CCC （His2Pro） mutations caused changes in the physical and chemical properties of amino acids. Each sequence alteration was identified in sporadic IPF patients, control specimens （pneumonia patients and healthy persons）. Genotype frequencies and allele frequencies of codon 238 in exon 6 of SFTPA1 were noted significantly higher in patients with IPF than those in other two control subjects. The computational protein structure prediction by protein homology modeling confirmed differences in three-dimensional structure between mutant SFTPA1 and original SFTPAI. Conclusions Although the functions of the mutant candidate genes vary, these genes may ultimately result in damage to alveolar epithelial cells, initiating the progress of pulmonary fibrosis. In particular, while pathophysiological mechanisms need to be illustrated, the GIn238Lys missense variant of exon 6 in the SFTPA1 may have potential susceptibility in the development of IPF, which was shown in patients with sporadic IPF with a statistically higher frequency.