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

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

Bibliographical note

Funding Information:
The authors thank Marilyn Perry and Yuxiao Du for their work as Registry coordinators and we are grateful for the generous participation of our subjects. This work was supported by the Scleroderma Foundation New Investigator Award to Dr. Wu, and by the National Institutes of Health (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Centers of Research Translation (CORT) grant P50AR054144 to Dr. Mayes, NIH grant K23AR061436 to Dr. Assassi, NIH/NIAMS Scleroderma Family Registry and DNA Repository grant N01-AR02251 to Dr. Mayes, NIH/NIAMS grant AR055258 to Dr. Mayes, NIH National Center for Clinical and Translational Sciences grant 3UL1RR024148, Department of Defense Congressionally Directed Medical Research Program W81XWH-13-1-0452, Proposal number PR120687 to Dr. Mayes.

Publisher Copyright:
© 2016 Wu et al.


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


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