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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc. Methods: A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and analyzed for their association with SSc. Results: We found an association of SSc with the SNP rs6793295 in the LRRC34 gene (OR = 1.14, CI 95 % 1.03 to 1.25, p value = 0.009) and rs11191865 in the OBFC1 gene (OR = 1.09, CI 95 % 1.00 to 1.19, p value = 0.043) in the discovery cohort. Additionally, rs7934606 in MUC2 (OR = 1.24, CI 95 % 1.01 to 1.52, p value = 0.037) was associated with SSc-ILD defined by imaging. However, these associations failed to replicate in the validation cohort. Furthermore, SNPs rs2076295 in DSP (β = -2.29, CI 95 % -3.85 to -0.74, p value = 0.004) rs17690703 in SPPL2C (β = 2.04, CI 95 % 0.21 to 3.88, p value = 0.029) and rs1981997 in MAPT (β = 2.26, CI 95 % 0.35 to 4.17, p value = 0.02) were associated with percent predicted forced vital capacity (FVC%) even after adjusting for the anti-topoisomerase (ATA)-positive subset. However, these associations also did not replicate in the validation cohort. Conclusions: Our results add new evidence that SSc and SSc-related ILD are genetically distinct from IIP, although they share phenotypic similarities.

Original languageEnglish (US)
Article number20
JournalArthritis Research and Therapy
Issue number1
StatePublished - Jan 20 2016


  • Genetic susceptibility
  • Idiopathic interstitial pneumonia (IIP)
  • SSc-ILD

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology


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