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

Hirano, Chihiro; Ohshimo, Shinichiro; Horimasu, Yasushi; Iwamoto, Hiroshi; Fujitaka, Kazunori; Hamada, Hironobu; Hattori, Noboru; Shime, Nobuaki; Bonella, Francesco; Guzman, Josune; Costabel, Ulrich; Kohno, Nobuoki

doi:10.1016/j.rmed.2016.12.007

Cited by 28 publications

(23 citation statements)

References 21 publications

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“…MUC5B is only one genetic variant associated with the development of IIP. While our findings suggest that the MUC5B variant does not contribute to risk in myositis-ILD, it does not exclude other shared genetic risk factors [17]. Myositis-ILD is likely due to the interaction of multiple genetic risk factors and environmental exposures.…”

Section: Discussioncontrasting

confidence: 79%

Exploration of the MUC5B promoter variant and ILD risk in patients with autoimmune myositis

Johnson

Rosen

Lloyd

et al. 2017

Respiratory Medicine

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Interstitial lung disease (ILD) is common in patients with autoimmune myositis but factors that determine susceptibility are unknown. Familial and sporadic idiopathic pulmonary fibrosis (IPF) are strongly associated with a single nucleotide polymorphism in the promoter region of MUC5B (rs35705950). We sought to determine the relationship between MUC5B polymorphism expression and myositis-ILD. The MUC5B minor allele frequency (MAF) was examined in 402 European American participants; 60 with idiopathic interstitial pneumonia (IIP), 208 with myositis-ILD, and 134 unaffected controls. The MUC5B minor allele frequency was 26%, 8%, and 7% in those with non-myositis ILD, myositis-ILD, and unaffected controls, respectively. The MUC5B variant was associated with IIP (OR 4.10; p < 0.001). The MUC5B polymorphism was not significantly associated with myositis-ILD (OR 1.08; p = 0.80)]. We found MUC5B MAFs in our IIP cohort similar to published frequencies for subjects with familial and sporadic IPF. Overall, the MUC5B promoter variant does not appear to contribute to ILD risk in myositis patients.

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Section: Discussioncontrasting

confidence: 79%

Exploration of the MUC5B promoter variant and ILD risk in patients with autoimmune myositis

Johnson

Rosen

Lloyd

et al. 2017

Respiratory Medicine

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“…In the meanwhile, Eisenhut et al () denoted FAM13A was associated with non‐small cell lung cancer (NSCLC) progression and controls tumor cell proliferation and survival. Hirano et al () reported the polymorphism of FAM13A gene had a significant association with the susceptibility to idiopathic pulmonary fibrosis, with severity of lung function impairment and with poor prognosis. However, studies about the FAM13A and other diseases have not been reported, including liver cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

High expression of FAM13A was associated with increasing the liver cirrhosis risk

Zhang

Wang

et al. 2019

Molec Gen & Gen Med

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Aim Liver cirrhosis is a consequence of chronic liver disease, and it may be caused by multiple influences of both genetic and environmental factors. Family with sequence similarity 13 member A ( FAM13A ) has been previously associated with lung function in several lung diseases, including chronic obstructive pulmonary disease, asthma, lung cancer, and pulmonary fibrosis. The aim of this study was to explore whether FAM13A polymorphisms confer susceptibility to liver cirrhosis. Methods FAM13A expression was evaluated in liver cirrhosis tissues by immunohistochemistry staining. The relationship between FAM13A gene polymorphism and liver cirrhosis was determined by association analysis. The genotypes were assessed in the Agena MassARRAY platform. Statistical analysis was performed using chi‐squared test/Fisher's exact test, genetic model analysis, and haplotype analysis. Results The results showed that the expression of FAM13A is obvious higher in the liver cirrhosis tissue cells than in the normal liver tissue cells. Moreover, association analysis results indicated that the minor allele “A” of rs3017895 was positively associated with high risk of liver cirrhosis in the allele model by the chi‐squared test (OR = 1.32, 95%CI = 1.03–1.68, p = 0.028). Logistic regression analyses revealed that the risk of liver cirrhosis was significantly higher in subjects with the G/A‐G/G genotype of rs3017895 than those with A/A genotype under the dominant model and log additive model, and the T/A‐A/A genotype of rs1059122 was positively associated with higher liver cirrhosis than T/T genotype based on dominant model respectively. In addition, haplotype analysis showed that the G‐A haplotype of rs3017895‐rs1059122 of the FAM13A gene significantly increased the risk of liver cirrhosis. Conclusion Our findings demonstrated that the high expression of FAM13A may be associated with an increased risk of liver cirrhosis.

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“…Recent genome-wide association studies identified family with sequence similarity 13, member A (FAM13A) gene as a genetic locus associated with pulmonary function [4], and it is known to be associated with lung diseases including chronic obstructive pulmonary disease (COPD) [5], asthma [6] and pulmonary fibrosis [7][8][9]. Moreover, causative role of FAM13A in the development of COPD has been revealed.…”

Section: Introductionmentioning

confidence: 99%

Loss of family with sequence similarity 13, member A exacerbates pulmonary hypertension through accelerating endothelial-to-mesenchymal transition

et al. 2020

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Pulmonary hypertension is a progressive lung disease with poor prognosis due to the consequent right heart ventricular failure. Pulmonary artery remodeling and dysfunction are culprits for pathologically increased pulmonary arterial pressure, but their underlying molecular mechanisms remain to be elucidated. Previous genome-wide association studies revealed a significant correlation between the genetic locus of family with sequence similarity 13, member A (FAM13A) and various lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis; however whether FAM13A is also involved in the pathogenesis of pulmonary hypertension remained unknown. Here, we identified a significant role of FAM13A in the development of pulmonary hypertension. FAM13A expression was reduced in the lungs of mice with hypoxia-induced pulmonary hypertension. We identified that FAM13A was expressed in lung vasculatures, especially in endothelial cells. Genetic loss of FAM13A exacerbated pulmonary hypertension in mice exposed to chronic hypoxia in association with deteriorated pulmonary artery remodeling. Mechanistically, FAM13A decelerated endothelial-to-mesenchymal transition potentially by inhibiting β-catenin signaling in pulmonary artery endothelial cells. Our data revealed a protective role of FAM13A in the development of pulmonary hypertension, and therefore increasing and/or preserving FAM13A expression in pulmonary artery endothelial cells is an attractive therapeutic strategy for the treatment of pulmonary hypertension.

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

Abstract: FAM13A gene polymorphism showed a significant association with the susceptibility to IPF, with severity of lung function impairment and with poor prognosis.

Cited by 28 publications

References 21 publications

Exploration of the MUC5B promoter variant and ILD risk in patients with autoimmune myositis

Exploration of the MUC5B promoter variant and ILD risk in patients with autoimmune myositis

High expression of FAM13A was associated with increasing the liver cirrhosis risk

Loss of family with sequence similarity 13, member A exacerbates pulmonary hypertension through accelerating endothelial-to-mesenchymal transition

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