Song Seung Taek, Kim Song Soo, Kim Ji Young, Lee So Young, Kim Kwangwoo, Kwon In Sun, Kim Ji Na, Park Won Hong, Yoo In Seol, Yoo Su-Jin, Kim Jin Hyun, Kang Seong Wook, Shim Seung-Cheol
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.
Lung. 2016 Oct;194(5):745-53. doi: 10.1007/s00408-016-9916-x. Epub 2016 Jul 2.
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.
肺部疾病(LD)是类风湿关节炎(RA)常见的关节外表现。然而,关于类风湿关节炎相关肺部疾病(RA-LD)易感性相关因素的了解甚少。本研究的目的是调查肽基精氨酸脱亚氨酶4(PADI4)和人白细胞抗原DRB1(HLA-DRB1)等位基因的单核苷酸多态性(SNP)是否与RA-LD相关。
收集116例符合1987年美国风湿病学会分类标准的连续RA患者的血样和临床资料。采用胸部高分辨率计算机断层扫描诊断RA-LD。对所有患者进行PADI4和HLA-DRB1等位基因的SNP基因分型,并分析与4位数字HLA分型相对应的HLA蛋白的完整氨基酸序列。连续变量采用独立t检验(或曼-惠特尼检验)分析,分类变量采用卡方检验(或费舍尔精确检验)和趋势检验分析,采用逻辑回归分析。
94例(81.0%)RA患者患有LD,其中8例(6.9%)患有间质性肺疾病(ILD),92例(79.3%)存在气道异常,其中64例(55.2%)表现为支气管扩张,47例(40.5%)显示支气管壁增厚。padi4_92的隐性基因型易患气道异常(比值比[OR]=2.22,95%置信区间[CI]=1.05-4.49,p=0.034)。HLA-DRB1序列第9位的色氨酸与RA-ILD的易感性相关(OR=22.89,95%CI=1.20-432.56,p=0.037)。
PADI4多态性和HLA-DRB1等位基因分别可能对RA患者气道异常和ILD发生发展有不同影响。