title: Genetic characterization of a Chinese family with familial idiopathic pulmonary fibrosis.
abstract: 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 (Gln238Lys) 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 SFTPA1.
  
  
  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 Gln238Lys 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.
authors.affiliation: Department of Respiratory Medicine, Hainan Branch of Chinese People's Liberation Army General Hospital, Sanya, Hainan 572000, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Chen
authors.forename: Long-Xiang
authors.initials: LX
authors.lastname: Su
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Xie
mesh_terms: D000328:Adult; D002681:China; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; C445842:SFTPA1 protein, human