Chihiro Hirano1, Shinichiro Ohshimo2, Yasushi Horimasu3, Hiroshi Iwamoto4, Kazunori Fujitaka5, Hironobu Hamada6, Noboru Hattori7, Nobuaki Shime8, Francesco Bonella9, Josune Guzman10, Ulrich Costabel11, Nobuoki Kohno12. 1. Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: cyamaoka62@hiroshoma-u.ac.jp. 2. 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. 3. Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: yasushi17@hiroshima-u.ac.jp. 4. Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: hir@hiroshima-u.ac.jp. 5. Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: fujikazu@hiroshima-u.ac.jp. 6. 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. 7. Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: nhattori@hiroshima-u.ac.jp. 8. Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan. Electronic address: nshime@hiroshima-u.ac.jp. 9. Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany. Electronic address: francesco.bonella@ruhrlandklinik.uk-essen.de. 10. General and Experimental Pathology, Ruhr University Bochum, Germany. Electronic address: josune.guzman@ruhr-uni-bochum.de. 11. Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany. Electronic address: ulrich.costabel@ruhrlandklinik.uk-essen.de. 12. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: FAM13A gene polymorphism showed a significant association with the susceptibility to IPF, with severity of lung function impairment and with poor prognosis.
BACKGROUND: 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 FAM13Ars2609255 and idiopathic interstitial pneumonias in a Caucasian population. However, the relationship between rs2609255 polymorphism and prognosis in idiopathic interstitial pneumonias has not been investigated. METHODS: 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. RESULTS: 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). CONCLUSIONS:FAM13A gene polymorphism showed a significant association with the susceptibility to IPF, with severity of lung function impairment and with poor prognosis.