关键词: 结缔组织病, 肺疾病, 间质性, 黏蛋白-1, KL-6, 肺功能, 相关性分析

Abstract: Background　Interstitial lung disease seriously affects the prognosis of patients with connective tissue disease（CTD）.Recent studies have suggested that Krebs von den Lungen-6（KL-6）secreted by human typeⅡ alveolar epithelial cells is a sensitive biomarker of interstitial lung disease.MUC1 rs4072037 polymorphism is related to individual differences in KL-6 levels，but there are no rs4072037 of MUC1 gene related data in patients with connective tissue disease-associated interstitial lung disease（CTD-ILD），and the relationship of rs4072037 of MUC1 gene with serum KL-6 levels is not clear.Objective　This study was aimed at investigating the correlation of MUC1 rs4072037 polymorphism with serum KL-6 and pulmonary function and its prognostic value in patients with CTD-ILD.Methods　We retrospectively studied 48 CTD-ILD inpatients（CTD-ILD group）and 13 inpatients with CTD（CTD group）recruited from Department of Rheumatology and Immunology，the First Affiliated Hospital of University of South China，and 30 healthy volunteers（control group）recruited from outpatient health examinees of the hospital from January 2015 to December 2018.We collected their lung function parameters〔FVC%pred，FEV1%pred，TLC%pred，diffusing capacity for carbon monoxide（DLCO%pred），PaO2，alveolar-arterial oxygenation gradient（A-aDO2）〕，and serum KL-6，LDH and MUC1 rs4072037 polymorphism.Kaplan Meier method was used to draw survival curves， and log rank test was used to evaluate the difference between survival curves.Cox proportional hazards model was used to explore factors independently associated with CTD-ILD.C- statistics analysis was used to analyze the testing power of the predictive model.Results　Compared with the control group，CTD and CTD-ILD groups had much lower FVC%pred，FEV1%pred and PaO2 and higher A-aDO2，serum KL-6 and LDH（P<0.05）.The DLCO%pred of the CTD-ILD group was lower than that of other two groups（P<0.05）.A-aDO2 in CTD-ILD group was higher than that in CTD group（P<0.05）.In CTD-ILD group，there were 22 cases with A/A genotype and 26 with A/G genotype，while in control group，there were 9 with A/A genotype，12 with A/G genotype，and 9 with G/G genotype，indicating significant intergroup difference in MUC1 rs4072037 polymorphism（χ2=16.325，P<0.001）.CTD-ILD patients with A/A genotype had higher serum KL-6 level〔（8.09±1.68）U/L vs（2.40±4.64） U/L〕（t=3.748，P=0.007）and LDH〔（372±40 ）U/L vs（266±23 ）U/L〕（t=2.124，P=0.030）than those with A/G genotype.CTD-ILD patients with A/G genotype had lower A-aDO2〔（35±3）mm Hg vs（45±4）mm Hg〕and but higher DLCO%pred〔（58%±3%）vs（40%±6%）〕than those with A/A genotype（t=2.377，2.778，P=0.027，0.012）.The cumulative disease progression rate of CTD-ILD patients with A/A genotype and those with A/G genotype was different（χ2=9.242，P=0.008）.Multivariate analysis with Cox proportional hazards model showed that，MUC1 rs4072037（G）was an influencing factor of the remission rate 〔HR=5.43，95%CI（1.2，25.6），P=0.025〕.C-statistics indicated that rs4072037（G）could predict the clinical remission rate in a model with covariates（P=0.021）.Conclusion　MUC1 rs4072037 polymorphism may be closely associated with serum KL-6，pulmonary function and prognosis in patients with CTD-ILD，and can predicte the clinical remission rate.

Key words: Connective tissue disease；Lung diseases, interstitial；Interstitial lung disease；Mucin-1；KL-6；Pulmonary function；Correlation analysis