Association of Single Nucleotide Polymorphisms of PADI4 and HLA-DRB1 Alleles with Susceptibility to Rheumatoid Arthritis-Related Lung Diseases

• DOI: 10.1007/s00408-016-9916-x
• Publication Date: 2016-07-02T04:09:09Z
• Authors: Seung Taek Song; Song Soo Kim; Ji Young Kim; So Young Lee; Kwangwoo Kim; In Sun Kwon; Ji Na Kim; Won Hong Park; In Seol Yoo; Su-Jin Yoo; Jin Hyun Kim; Seong Wook Kang; Seung-Cheol Shim
• Keywords: Adult; Male; Genotype; Bronchi; Middle Aged; Polymorphism, Single Nucleotide; Bronchiectasis; 3. Good health; Arthritis, Rheumatoid; 03 medical and health sciences; 0302 clinical medicine; Protein-Arginine Deiminase Type 4; Protein-Arginine Deiminases; Humans; Female; Genetic Predisposition to Disease; Respiratory System Abnormalities; Lung Diseases, Interstitial; Aged; HLA-DRB1 Chains

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.