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Arthritis Res Ther. 2016 Jan 20;18:20. doi: 10.1186/s13075-016-0923-3.

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

Author information

1
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Minghua.wu@uth.tmc.edu.
2
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Shervin.assassi@uth.tmc.edu.
3
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Gloria.SalazarCintora@uth.tmc.edu.
4
Department of Pediatrics, The University of Texas Mcgovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Claudia.Pedroza@uth.tmc.edu.
5
Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, 1 Rope Ferry Road, Hanover, NH, 03755, USA. Olga.Y.Gorlova@dartmouth.edu.
6
Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, 1 Rope Ferry Road, Hanover, NH, 03755, USA. vwchen001@gmail.com.
7
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Julio.Charles@uth.tmc.edu.
8
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. miranda.l.taing@uth.tmc.edu.
9
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Kelley.Liao@uth.tmc.edu.
10
Division of Rheumatology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview circle, Baltimore, MD, 21224, USA. fwig@jhmi.edu.
11
Division of Rheumatology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview circle, Baltimore, MD, 21224, USA. lhummers@jhmi.edu.
12
Division of Rheumatology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview circle, Baltimore, MD, 21224, USA. Ami.Shah@jhmi.edu.
13
Division of Rheumatology, Northwestern University Feinberg School of Medicine, 240 East Huron Street, Chicago, IL, 60611, USA. m-hinchcliff@northwestern.edu.
14
Department of Internal Medicine, Division of Rheumatology, University of Michigan Health Center, 300 North Ingalls Street, Ann Arbor, MI, 48109, USA. khannad@med.umich.edu.
15
Department of Internal Medicine, Division of Rheumatology, University of Michigan Health Center, 300 North Ingalls Street, Ann Arbor, MI, 48109, USA. eschiopu@med.umich.edu.
16
Department of Internal Medicine, Division of Rheumatology, University of Michigan Health Center, 300 North Ingalls Street, Ann Arbor, MI, 48109, USA. kphill@med.umich.edu.
17
Division of Rheumatology, University of California Los Angeles, 1000 Veterans Avenue, Los Angeles, CA, 90024, USA. DEFurst@mednet.ucla.edu.
18
Division of Rheumatology, Georgetown University Medical Center, 3800 Reservoir Road, Washington, MD, 20007, USA. steenv@georgetown.edu.
19
Division of Rheumatology, McGill University, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada. murray.baron@jgh.mcgill.ca.
20
Division of Rheumatology, McGill University, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada. marie.hudson@mcgill.ca.
21
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. xiaodong.zhou@uth.tmc.edu.
22
Division of Rheumatology, St. Joseph's Health Care, University of Western Ontario, 268 Grosvenor Street, London, ON, Canada. janet.pope@sjhc.london.on.ca.
23
Division of Rheumatology, University of Alberta, 11405-87 Avenue, Edmonton, AB, T6G 1C9, Canada. sameitjones@shaw.ca.
24
Division of Rheumatology, Moncton Hospital, 135 MacBeath Avenue, Moncton, NB, E1C 6Z8, Canada. pedocher@serha.ca.
25
Division of Rheumatology, McMaster University at Hamilton, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada. naderkhalidi@sympatico.ca.
26
Division of Rheumatology, University of Manitoba, 820 Sherbrook Street, Winnipeg, MB, R3A 1R9, Canada. drobinson@hsc.mb.ca.
27
Division of Rheumatology, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA. rsimms@bu.edu.
28
Division of Rheumatology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC, 29425, USA. silverr@musc.edu.
29
Division of Rheumatology, University of Utah, 30 North 1900 East, Salt Lake City, UT, 84132, USA. Tracy.frech@hsc.utah.edu.
30
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 1825 University Boulevard, Birmingham, AB, 35294, USA. bjf@uab.edu.
31
Division of Rheumatology, University of Calgary Cumming School of Medicine, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. fritzler@ucalgary.ca.
32
Division of Rheumatology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA. jmolitor@umn.edu.
33
Division of Rheumatology, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA. Segal017@umn.edu.
34
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Malahat.Movahedian@uth.tmc.edu.
35
Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Cientıficas, C/Ventanilla 11, 18001, Granada, Spain. martin@ipb.csic.es.
36
Division of Rheumatology, Northwestern University Feinberg School of Medicine, 240 East Huron Street, Chicago, IL, 60611, USA. j-varga@northwetern.edu.
37
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas McGovern Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA. Maureen.D.Mayes@uth.tmc.edu.

Abstract

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.

PMID:
26792595
PMCID:
PMC4719560
DOI:
10.1186/s13075-016-0923-3
[Indexed for MEDLINE]
Free PMC Article

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