FAM13A polymorphism as a prognostic factor in patients with idiopathic pulmonary fibrosis

Respir Med. 2017 Feb:123:105-109. doi: 10.1016/j.rmed.2016.12.007. Epub 2016 Dec 22.

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.

Keywords: Family with sequence similarity 13; Idiopathic pulmonary fibrosis; Member A (FAM13A); Single nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Aged
  • Case-Control Studies
  • Female
  • GTPase-Activating Proteins / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Idiopathic Pulmonary Fibrosis / diagnosis
  • Idiopathic Pulmonary Fibrosis / genetics*
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prognosis

Substances

  • FAM13A protein, human
  • GTPase-Activating Proteins