目的应用孟德尔随机化法(Mendelianrandomization,MR),以单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量,探讨皮肤和黏膜病变为特征的病毒感染与皮肌炎(dermatomyositis,DM)的因果关系。方法从IEU Open GWAS project...目的应用孟德尔随机化法(Mendelianrandomization,MR),以单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量,探讨皮肤和黏膜病变为特征的病毒感染与皮肌炎(dermatomyositis,DM)的因果关系。方法从IEU Open GWAS project网站中获得近3a、样本量最大的皮肤和黏膜病变为特征的病毒感染(finn-b-AB1_VIRAL_SKIN_MUCOUS_MEMBRANE)及DM(finn-b-M13_DERMATOPOLY)的全基因组关联研究(genome-wide association study,GWAS)数据。从finn-b-AB1_VIRAL_SKIN_MUCOUS_MEMBRANE中筛选与皮肤和黏膜病变为特征的病毒感染高度相关的SNP(以P<5×10^(-8)作为筛选条件,连锁不平衡区域宽度为10000 kb,连锁不平衡系数r2为0.001)。从finn-b-M13_DERMATOPOLY中提取与皮肤和黏膜病变相关的高度连锁性SNP,最小r2值>0.8。汇集两个数据集,去除与DM直接相关的SNP,将包括rs10051884、rs9438624、rs62194265等位点的73个SNP作为工具变量,采用MR-Egger回归、随机效应逆方差加权法(inverse-variance weighted,IVW)及加权中位数法回归模型,分析皮肤和黏膜病变为特征的病毒感染与DM的因果联系。结果GWAS数据均来源于欧洲人群,不限男女。MR-Egger的回归截距项是-0.022(P=0.644),这提示筛选出的SNP同DM间不存在基因多效性。MR-Egger回归、IVW、加权中位数法的OR(95%CI)分别为1.676(0.808~3.480)、1.362(0.865~2.145)、1.439(1.021~2.029);由于存在异质性(Q=93.823,P=0.036),故关注随机效应IVW的结果。结论皮肤和黏膜病变为特征的病毒感染是DM的危险因素。展开更多
特发性炎症性肌病(IIM)中,肺间质改变是其中的一个重要特征,尤其多见于皮肌炎(DM)和临床无肌病性皮肌炎(CADM)患者。这些肺间质改变可分为快速进展型间质性肺病(RP-ILD)和慢性间质性肺炎(CIP),其中RP-ILD患者会在短期内经历急性、进展...特发性炎症性肌病(IIM)中,肺间质改变是其中的一个重要特征,尤其多见于皮肌炎(DM)和临床无肌病性皮肌炎(CADM)患者。这些肺间质改变可分为快速进展型间质性肺病(RP-ILD)和慢性间质性肺炎(CIP),其中RP-ILD患者会在短期内经历急性、进展性的弥漫性肺损伤,预后较差。由于疾病早期往往缺乏明显或有特异性的呼吸道症状,且肺功能检查在间质性肺病(ILD)诊断中的特异性和灵敏性有限,因此早期识别风险因素和实施筛查对于疾病管理至关重要。探寻DM相关间质性肺病(DM-ILD)的风险因素和临床特征,能够为疾病的诊断和治疗提供更多依据,有助于稳定甚至改善肺功能,进而改善患者的预后。Interstitial lung involvement is a significant characteristic in idiopathic inflammatory myopathies (IIM), particularly prevalent among patients with dermatomyositis (DM) and clinically amyopathic dermatomyositis (CADM). These interstitial lung alterations can be categorized into rapidly progressive interstitial lung disease (RP-ILD) and chronic interstitial pneumonia (CIP). Patients with RP-ILD experience acute, progressive diffuse lung injury over a short period, leading to poor prognosis. Due to the early stages of the disease often lacking distinct or specific respiratory symptoms and the limited specificity and sensitivity of pulmonary function tests in the diagnosis of interstitial lung disease (ILD), early identification of risk factors and implementation of screening are crucial for disease management. Investigating the risk factors and clinical features associated with DM-related interstitial lung disease (DM-ILD) can provide additional evidence for the diagnosis and treatment of the disease, which may help stabilize or even improve lung function, thereby improving patient prognosis.展开更多
文摘目的应用孟德尔随机化法(Mendelianrandomization,MR),以单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量,探讨皮肤和黏膜病变为特征的病毒感染与皮肌炎(dermatomyositis,DM)的因果关系。方法从IEU Open GWAS project网站中获得近3a、样本量最大的皮肤和黏膜病变为特征的病毒感染(finn-b-AB1_VIRAL_SKIN_MUCOUS_MEMBRANE)及DM(finn-b-M13_DERMATOPOLY)的全基因组关联研究(genome-wide association study,GWAS)数据。从finn-b-AB1_VIRAL_SKIN_MUCOUS_MEMBRANE中筛选与皮肤和黏膜病变为特征的病毒感染高度相关的SNP(以P<5×10^(-8)作为筛选条件,连锁不平衡区域宽度为10000 kb,连锁不平衡系数r2为0.001)。从finn-b-M13_DERMATOPOLY中提取与皮肤和黏膜病变相关的高度连锁性SNP,最小r2值>0.8。汇集两个数据集,去除与DM直接相关的SNP,将包括rs10051884、rs9438624、rs62194265等位点的73个SNP作为工具变量,采用MR-Egger回归、随机效应逆方差加权法(inverse-variance weighted,IVW)及加权中位数法回归模型,分析皮肤和黏膜病变为特征的病毒感染与DM的因果联系。结果GWAS数据均来源于欧洲人群,不限男女。MR-Egger的回归截距项是-0.022(P=0.644),这提示筛选出的SNP同DM间不存在基因多效性。MR-Egger回归、IVW、加权中位数法的OR(95%CI)分别为1.676(0.808~3.480)、1.362(0.865~2.145)、1.439(1.021~2.029);由于存在异质性(Q=93.823,P=0.036),故关注随机效应IVW的结果。结论皮肤和黏膜病变为特征的病毒感染是DM的危险因素。
文摘特发性炎症性肌病(IIM)中,肺间质改变是其中的一个重要特征,尤其多见于皮肌炎(DM)和临床无肌病性皮肌炎(CADM)患者。这些肺间质改变可分为快速进展型间质性肺病(RP-ILD)和慢性间质性肺炎(CIP),其中RP-ILD患者会在短期内经历急性、进展性的弥漫性肺损伤,预后较差。由于疾病早期往往缺乏明显或有特异性的呼吸道症状,且肺功能检查在间质性肺病(ILD)诊断中的特异性和灵敏性有限,因此早期识别风险因素和实施筛查对于疾病管理至关重要。探寻DM相关间质性肺病(DM-ILD)的风险因素和临床特征,能够为疾病的诊断和治疗提供更多依据,有助于稳定甚至改善肺功能,进而改善患者的预后。Interstitial lung involvement is a significant characteristic in idiopathic inflammatory myopathies (IIM), particularly prevalent among patients with dermatomyositis (DM) and clinically amyopathic dermatomyositis (CADM). These interstitial lung alterations can be categorized into rapidly progressive interstitial lung disease (RP-ILD) and chronic interstitial pneumonia (CIP). Patients with RP-ILD experience acute, progressive diffuse lung injury over a short period, leading to poor prognosis. Due to the early stages of the disease often lacking distinct or specific respiratory symptoms and the limited specificity and sensitivity of pulmonary function tests in the diagnosis of interstitial lung disease (ILD), early identification of risk factors and implementation of screening are crucial for disease management. Investigating the risk factors and clinical features associated with DM-related interstitial lung disease (DM-ILD) can provide additional evidence for the diagnosis and treatment of the disease, which may help stabilize or even improve lung function, thereby improving patient prognosis.
