Abstract

Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD +) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD +), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T > C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients.

Details

Title
Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome
Author
Remuzgo-Martínez, Sara 1 ; Atienza-Mateo Belén 2 ; Gonzalo, Ocejo-Vinyals J 3 ; Genre Fernanda 1 ; Pulito-Cueto Verónica 1 ; Mora-Cuesta, Víctor M 4 ; Iturbe-Fernández, David 4 ; Lera-Gómez, Leticia 1 ; Pérez-Fernández, Raquel 1 ; Prieto-Peña, Diana 5 ; Irure Juan 3 ; Romero-Bueno Fredeswinda 6 ; Sanchez-Pernaute, Olga 6 ; Alonso-Moralejo, Rodrigo 7 ; Nuño, Laura 8 ; Bonilla Gema 8 ; Vicente-Rabaneda, Esther F 9 ; Grafia Ignacio 10 ; Prieto-González, Sergio 10 ; Narvaez, Javier 11 ; Trallero-Araguas Ernesto 12 ; Selva-O’Callaghan Albert 13 ; Ortego-Centeno Norberto 14 ; Pérez-Gómez Nair 15 ; Mera, Antonio 15 ; Martínez-Barrio, Julia 16 ; Moriano Clara 17 ; Díez Elvira 17 ; Calvo-Alén, Jaime 18 ; Balsa Alejandro 8 ; Ussetti María Piedad 19 ; Laporta Rosalía 19 ; Berastegui Cristina 20 ; Solé Amparo 21 ; Gualillo Oreste 22 ; Cavagna Lorenzo 23 ; Cifrián, José M 24 ; Renzoni, Elisabetta A 25 ; Castañeda Santos 9 ; López-Mejías, Raquel 1 ; González-Gay, Miguel A 26 

 IDIVAL, Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Diseases of the Musculoskeletal System, Santander, Spain (GRID:grid.484299.a) 
 IDIVAL, Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Diseases of the Musculoskeletal System, Santander, Spain (GRID:grid.484299.a); Hospital Universitario Marqués de Valdecilla, López Albo’ Post-Residency Programme, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262); Hospital Universitario Marqués de Valdecilla, Rheumatology Department, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262) 
 Hospital Universitario Marqués de Valdecilla, Department of Immunology, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262) 
 IDIVAL, Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Diseases of the Musculoskeletal System, Santander, Spain (GRID:grid.484299.a); Hospital Universitario Marqués de Valdecilla, Pneumology Department, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262) 
 IDIVAL, Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Diseases of the Musculoskeletal System, Santander, Spain (GRID:grid.484299.a); Hospital Universitario Marqués de Valdecilla, Rheumatology Department, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262) 
 Hospital Universitario Fundación Jiménez Díaz, Rheumatology Department, Madrid, Spain (GRID:grid.419651.e) (ISNI:0000 0000 9538 1950) 
 Hospital Universitario 12 de Octubre, Lung Transplant Unit, Madrid, Spain (GRID:grid.144756.5) (ISNI:0000 0001 1945 5329) 
 Hospital Universitario La Paz, Rheumatology Department, Madrid, Spain (GRID:grid.81821.32) (ISNI:0000 0000 8970 9163) 
 IIS-Princesa, Rheumatology Department, Hospital de la Princesa, Madrid, Spain (GRID:grid.476442.7) 
10  Universidad de Barcelona, Department of Autoimmune Diseases, Hospital Clínico de Barcelona, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247) 
11  Hospital Universitario de Bellvitge, Rheumatology Department, Barcelona, Spain (GRID:grid.411129.e) (ISNI:0000 0000 8836 0780) 
12  Hospital Universitario Vall d’Hebron, Rheumatology Unit, Barcelona, Spain (GRID:grid.411083.f) (ISNI:0000 0001 0675 8654) 
13  Hospital Universitario Vall d’Hebron, Systemic Autoimmune Diseases Unit, Barcelona, Spain (GRID:grid.411083.f) (ISNI:0000 0001 0675 8654) 
14  Universidad de Granada, Department of Medicine, Granada, Spain (GRID:grid.4489.1) (ISNI:0000000121678994) 
15  Instituto de Investigación Sanitaria-Hospital Clínico Universitario de Santiago, Division of Rheumatology, Santiago de Compostela, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945) 
16  Hospital General Universitario Gregorio-Marañón, Department of Rheumatology, Madrid, Spain (GRID:grid.410526.4) (ISNI:0000 0001 0277 7938) 
17  Complejo Asistencial Universitario de León, Division of Rheumatology, León, Spain (GRID:grid.411969.2) (ISNI:0000 0000 9516 4411) 
18  Hospital Universitario Araba, Rheumatology Division, Vitoria/Gasteiz, Spain (GRID:grid.468902.1) (ISNI:0000 0004 1773 0974) 
19  Hospital Universitario Puerta de Hierro, Pneumology Department, Majadahonda, Spain (GRID:grid.73221.35) (ISNI:0000 0004 1767 8416) 
20  Hospital Universitario Vall d’Hebron, Universidad Autónoma de Barcelona, Pneumology Department, Barcelona, Spain (GRID:grid.411083.f) (ISNI:0000 0001 0675 8654) 
21  Hospital Universitario y Politécnico La Fe, Lung Transplant and Cystic Fibrosis Unit, Valencia, Spain (GRID:grid.84393.35) (ISNI:0000 0001 0360 9602) 
22  Hospital Clínico Universitario de Santiago, SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago de Compostela, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945) 
23  University and IRCCS Policlinico S. Matteo Foundation, Division of Rheumatology, Pavia, Italy (GRID:grid.419425.f) (ISNI:0000 0004 1760 3027) 
24  IDIVAL, Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Diseases of the Musculoskeletal System, Santander, Spain (GRID:grid.484299.a); Hospital Universitario Marqués de Valdecilla, Pneumology Department, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262); Universidad de Cantabria, School of Medicine, Santander, Spain (GRID:grid.7821.c) (ISNI:0000 0004 1770 272X) 
25  Imperial College London, Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
26  IDIVAL, Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Diseases of the Musculoskeletal System, Santander, Spain (GRID:grid.484299.a); Hospital Universitario Marqués de Valdecilla, Rheumatology Department, Santander, Spain (GRID:grid.411325.0) (ISNI:0000 0001 0627 4262); Universidad de Cantabria, School of Medicine, Santander, Spain (GRID:grid.7821.c) (ISNI:0000 0004 1770 272X); University of the Witwatersrand, Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, Johannesburg, South Africa (GRID:grid.11951.3d) (ISNI:0000 0004 1937 1135) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2599273154
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.