Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: a case control study in Caucasian patients

Wu, Minghua; Assassi, Shervin; Salazar, Gloria A.; Pedroza, Claudia; Gorlova, Olga Y.; Chen, Wei V.; Charles, Julio; Taing, Miranda L.; Liao, Kelley Z.; Wigley, Fredrick M.; Hummers, Laura K.; Shah, Ami A.; Hinchcliff, Monique; Khanna, Dinesh; Schiopu, Elena; Phillips, Kristine; Fürst, Daniel E.; Steen, Virginia D.; Baron, Murray; Hudson, Marie; Zhou, Xiaodong; Pope, Janet; Jones, Niall; Docherty, Peter; Khalidi, Nader; Robinson, David; Simms, Robert W.; Silver, Richard M.; Frech, Tracy; Fessler, Barri J.; Fritzler, Marvin J.; Molitor, Jerry A.; Segal, Barbara; Movahedian, Malahat; Martı́n, Javier; Varga, John; Mayes, Maureen D.

doi:10.1186/s13075-016-0923-3

Cited by 19 publications

(15 citation statements)

References 15 publications

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“…SSc-ILD shares some clinical features and pathogenesis with idiopathic pulmonary fibrosis (IPF) [57], although there are also key differences in disease morphological pattern and survival [58,59]. A number of genetic associations have been found with IPF, however, none of these, including the strongly associated MUC5B variant, are associated with SSc-ILD, suggesting that the genetic basis of the two diseases is different [60][61][62]. The fact that immunosuppressants are observed to stabilise disease in the majority of patients with progressive lung fibrosis in the context of SSc suggests that immune mediated pathways are key in driving the fibrotic process, but how this translates into genetic predisposition will require further study.…”

Section: Discussionmentioning

confidence: 99%

Genetic predictors of systemic sclerosis-associated interstitial lung disease: a review of recent literature

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Renzoni

2018

Eur J Hum Genet

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The interplay between genetic and environmental factors is likely involved in the pathogenesis of systemic sclerosis (SSc). Interstitial lung disease associated in the context of SSc (SSc-ILD) is associated with significant morbidity, and is the leading cause of death in SSc. The spectrum of SSc-ILD severity is wide, ranging from patients with only limited and inherently stable pulmonary involvement, to those with extensive and progressive pulmonary fibrosis. In order to provide accurate prognostic information for patients, and to initiate appropriate monitoring and treatment regimens, the ability to identify patients at risk of developing severe ILD early in the disease course is crucial. Identification of genetic variants involved in disease pathogenesis can not only potentially provide diagnostic/prognostic markers, but can also highlight dysregulated molecular pathways for therapeutic targeting. A number of genetic associations have been established for susceptibility to SSc, but far fewer studies have investigated genetic susceptibility to SSc-ILD specifically. In this review we present a summary of the studies assessing genetic associations with SSc-ILD.

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Section: Discussionmentioning

confidence: 99%

Genetic predictors of systemic sclerosis-associated interstitial lung disease: a review of recent literature

Stock

Renzoni

2018

Eur J Hum Genet

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“…[62][63][64] More broadly, the genetic susceptibility loci for IIPs identified in recent large genome-wide association studies were not consistently associated with SSc-ILD in a large study of 1,571 SSc patients. 65 Several HLA alleles have been associated with risk for SSc-ILD in various cohorts. 59,[66][67][68][69] Outside Fig.…”

Section: Genetics Of Ssc-ildmentioning

confidence: 99%

Systemic Sclerosis Associated Interstitial Lung Disease: A Comprehensive Overview

Mackintosh

Stainer

Barnett

et al. 2019

Semin Respir Crit Care Med

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Interstitial lung disease (ILD) is a common complication of systemic sclerosis (SSc). SSc-ILD adversely impacts quality of life and is currently the leading cause of death in this multisystem disease. Identifying clinically significant SSc-ILD is critically important. Accurate staging and prognostication remain difficult; however, significant advances have been made in the last decade. Evidence supports the need to treat patients with extensive and/or progressive SSc-ILD, while only a subset of patients with limited ILD may require treatment. Research is urgently required to allow improved prediction of patients at risk of ILD progression at an early point in the disease, and ideally prior to its onset, to allow prevention. The last decade has seen the publication of landmark clinical trials for SSc-ILD. More effective strategies with less toxicity are under investigation. For those with refractory or very advanced disease, studies into disease-specific palliative approaches are in their infancy. Lung transplantation as an option for SSc-ILD remains patient- and center-specific, with data to suggest equivalent outcomes to other fibrotic lung diseases, in carefully selected cases. This review aims to provide a comprehensive overview of all key aspects of SSc-ILD.

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“…However, despite some similarities with IPF and other idiopathic interstitial pneumonias (IIPs), SSc-ILD appears to be genetically distinct. Loci associated with IIPs tend to be involved with hostdefence, epithelial injury/dysfunction and wound healing [26]. The gain-of-function mucin 5B (MUC5B) promoter variant, the most consistent common genetic risk factor for IIPs, is not associated with SSc-ILD [27].…”

Section: Discussionmentioning

confidence: 99%

Defining genetic risk factors for scleroderma-associated interstitial lung disease

et al. 2020

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Although several genetic associations with scleroderma (SSc) are defined, very little is known on genetic susceptibility to SSc-associated interstitial lung disease (SSc-ILD). A number of common polymorphisms have been associated with SSc-ILD, but most have not been replicated in separate populations. Four SNPs in IRF5, and one in each of STAT4, CD226 and IRAK1, selected as having been previously the most consistently associated with SSc-ILD, were genotyped in 612 SSc patients, of European descent, of whom 394 had ILD. The control population (n = 503) comprised individuals of European descent from the 1000 Genomes Project. After Bonferroni correction, two of the IRF5 SNPs, rs2004640 (OR (95% CI)1.30 (1.10-1.54), p corr = 0.015) and rs10488631 (OR 1.48 (1.14-1.92), p corr = 0.022), and the STAT4 SNP rs7574865 (OR 1.43 (1.18-1.73), p corr = 0.0015) were significantly associated with SSc compared with controls. However, none of the SNPs were significantly different between patients with SSc-ILD and controls. Two SNPs in IRF5, rs10488631 (OR 1.72 (1.24-2.39), p corr = 0.0098), and rs2004640 (OR 1.39 (1.11-1.75), p corr = 0.03), showed a significant difference in allele frequency between controls and patients without ILD, as did STAT4 rs7574865 (OR 1.86 (1.45-2.38), p corr = 6.6 × 10 −6). A significant difference between SSc with and without ILD was only observed for STAT4 rs7574865, being less frequent in Previous publications The data in this manuscript has been presented at the European Respiratory Society Congress 2019 and at the British Thoracic Society Winter 2019 meeting, conference proceedings not yet published.

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Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: a case control study in Caucasian patients

Cited by 19 publications

References 15 publications

Genetic predictors of systemic sclerosis-associated interstitial lung disease: a review of recent literature

Genetic predictors of systemic sclerosis-associated interstitial lung disease: a review of recent literature

Systemic Sclerosis Associated Interstitial Lung Disease: A Comprehensive Overview

Defining genetic risk factors for scleroderma-associated interstitial lung disease

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