title: FAM13A polymorphism as a prognostic factor in patients with idiopathic pulmonary fibrosis.
abstract: Family with sequence similarity 13, member A (FAM13A) variants have been associated with susceptibility to chronic lung diseases. A recent genome-wide association study has shown an association between a polymorphism in FAM13A rs2609255 and idiopathic interstitial pneumonias in a Caucasian population. However, the relationship between rs2609255 polymorphism and prognosis in idiopathic interstitial pneumonias has not been investigated.
  
  
  
  Sixty-five patients with idiopathic pulmonary fibrosis (IPF) and 310 Japanese healthy volunteers were enrolled in this study. Genomic DNA was extracted from all subjects. rs2609255 was genotyped by a commercially available assay. The correlations between rs2609255 polymorphism and survival and the occurrence of acute exacerbation were evaluated.
  
  
  
  The frequency of the minor G allele was significantly higher in IPF patients (59.2%) than in controls (41.9%; OR = 1.78, 95% CI; 1.29-2.44, p < 0.001). The rs2609255 major T allele was associated with lower diffusing capacity of carbon monoxide values and higher composite physiologic index after adjustment for age, sex and smoking (β = -7.20, p = 0.005 and β = 5.59, p = 0.009, respectively). In the Kaplan-Meier analysis, the T allele carriers showed a significantly increased mortality compared to the non-carriers (p < 0.05). In the multivariate Cox-proportional hazards analysis, the T allele of rs2609255 was independently associated with poor survival (hazard ratio, 5.37; p = 0.031; 95% confidence interval, 1.16-24.82).
  
  
  
  FAM13A gene polymorphism showed a significant association with the susceptibility to IPF, with severity of lung function impairment and with poor prognosis.
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: cyamaoka62@hiroshoma-u.ac.jp.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hirano
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan; Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ohshimo
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: yasushi17@hiroshima-u.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Horimasu
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: hir@hiroshima-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwamoto
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: fujikazu@hiroshima-u.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fujitaka
authors.affiliation: Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address: hirohamada@hiroshima-u.ac.jp.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Hamada
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: nhattori@hiroshima-u.ac.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: nshime@hiroshima-u.ac.jp.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shime
authors.affiliation: Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany. Electronic address: francesco.bonella@ruhrlandklinik.uk-essen.de.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonella
authors.affiliation: General and Experimental Pathology, Ruhr University Bochum, Germany. Electronic address: josune.guzman@ruhr-uni-bochum.de.
authors.forename: Josune
authors.initials: J
authors.lastname: Guzman
authors.affiliation: Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany. Electronic address: ulrich.costabel@ruhrlandklinik.uk-essen.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan; Hiroshima Cosmopolitan University, Hiroshima, Japan. Electronic address: nokohno@hiroshima-u.ac.jp.
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
mesh_terms: D000208:Acute Disease; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: C570078:FAM13A protein, human; D020690:GTPase-Activating Proteins
keywords: Family with sequence similarity 13; Idiopathic pulmonary fibrosis; Member A (FAM13A); Single nucleotide polymorphism