title: Association of Single Nucleotide Polymorphisms of PADI4 and HLA-DRB1 Alleles with Susceptibility to Rheumatoid Arthritis-Related Lung Diseases.
abstract: Lung diseases (LD) are common extra-articular manifestations in rheumatoid arthritis (RA). However, little is known about factors associated with susceptibility to rheumatoid arthritis-related lung diseases (RA-LD). The aim of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) of PADI4 and HLA-DRB1 alleles were associated with RA-LD.
  
  
  
  Blood samples and clinical data were collected from 116 consecutive RA patients who satisfied the 1987 American College of Rheumatology classification criteria. RA-LD was diagnosed using high-resolution computed tomography of the chest. All patients were genotyped for SNPs of PADI4 and HLA-DRB1 alleles and analyzed for full amino acid sequence of the HLA protein corresponding to a 4-digit HLA typing. Data were analyzed by independent t test (or Mann-Whitney test) for continuous variables, Chi-square test (or Fisher's exact test) and trend test for categorical variables, and logistic regression analysis.
  
  
  
  Ninety-four (81.0 %) RA patients had LD, of which eight (6.9 %) had interstitial lung disease (ILD) and 92 (79.3 %) had airway abnormalities in which 64 (55.2 %) showed bronchiectasis and 47 (40.5 %) revealed bronchial wall thickening. The recessive genotype of padi4_92 was susceptible to airway abnormalities (OR = 2.22, 95 % CI = 1.05-4.49, p = 0.034). Tryptophan at position 9 of HLA-DRB1 sequence was associated with the susceptibility to RA-ILD (OR = 22.89, 95 % CI = 1.20-432.56, p = 0.037).
  
  
  
  PADI4 polymorphisms and HLA-DRB1 alleles could attribute differently to the development of airway abnormalities and ILD, respectively, in RA.
authors.affiliation: Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|Division of Rheumatology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea.
authors.forename: Seung Taek
authors.initials: ST
authors.lastname: Song
authors.affiliation: Department of Radiology, Chungnam National University School of Medicine, Daejeon, South Korea.
authors.forename: Song Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
authors.forename: Kwangwoo
authors.initials: K
authors.lastname: Kim
authors.affiliation: Clinical Trials Center, Chungnam National University Hospital, Daejeon, South Korea.
authors.forename: In Sun
authors.initials: IS
authors.lastname: Kwon
authors.affiliation: Department of Radiology, Chungnam National University School of Medicine, Daejeon, South Korea.
authors.forename: Ji Na
authors.initials: JN
authors.lastname: Kim
authors.affiliation: Department of Radiology, Chungnam National University School of Medicine, Daejeon, South Korea.
authors.forename: Won Hong
authors.initials: WH
authors.lastname: Park
authors.affiliation: Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|Division of Rheumatology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea.
authors.forename: In Seol
authors.initials: IS
authors.lastname: Yoo
authors.affiliation: Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|Division of Rheumatology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Yoo
authors.affiliation: Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|Division of Rheumatology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea.
authors.forename: Jin Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|Division of Rheumatology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea.
authors.forename: Seong Wook
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea. shimsc@cnuh.co.kr.|Division of Rheumatology, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea. shimsc@cnuh.co.kr.
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Shim
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications*; D001980:Bronchi / Q000473:pathology; D001987:Bronchiectasis / Q000209:etiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases / Q000235:genetics*; D015619:Respiratory System Abnormalities / Q000235:genetics*
chemical_list: D059811:HLA-DRB1 Chains; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
keywords: HLA-DRB1; Lung Diseases; Peptidyl Arginine Deiminase; Rheumatoid Arthritis