Jarenbäck Linnea, Frantz Sophia, Weidner Julie, Ankerst Jaro, Nihlén Ulf, Bjermer Leif, Wollmer Per, Tufvesson Ellen
Dept of Clinical Sciences Lund, Respiratory Medicine and Allergology, Lund University, Lund, Sweden.
Dept of Translational Science, Clinical Physiology, Lund University, Skåne University Hospital, Malmö, Sweden.
ERJ Open Res. 2022 May 16;8(2). doi: 10.1183/23120541.00668-2021. eCollection 2022 Apr.
Single nucleotide polymorphisms (SNPs) in various genes have been shown to associate with COPD, suggesting a role in disease pathogenesis. Sulfatase modifying factor (SUMF1) is a key modifier in connective tissue remodelling, and we have shown previously that several SNPs in are associated with COPD. The aim of this study was to investigate the association between SNPs and advanced lung function characteristics. Never-, former and current smokers with (n=154) or without (n=405) COPD were genotyped for 21 SNPs in and underwent spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide ( ) measurement and impulse oscillometry. Four SNPs (rs793391, rs12634248, rs2819590 and rs304092) showed a significantly decreased odds ratio of having COPD when heterozygous for the variance allele, together with a lower forced expiratory volume in 1 s (FEV) and FEV/forced vital capacity (FVC) ratio and an impaired peripheral resistance and reactance. Moreover, individuals homozygous for the variance allele of rs3864051 exhibited a strong association to COPD, a lower FEV/FVC, FEV and , and an impaired peripheral resistance and reactance. Other SNPs (rs4685744, rs2819562, rs2819561 and rs11915920) were instead associated with impaired lung volumes and exhibited a lower FVC, total lung capacity and alveolar volume, in individuals having the variance allele. Several SNPs in the gene are shown to be associated with COPD and impaired lung function. These genetic variants of may cause a deficient sulfation balance in the extracellular matrix of the lung tissue, thereby contributing to the development of COPD.
多种基因中的单核苷酸多态性（SNP）已被证明与慢性阻塞性肺疾病（COPD）相关，提示其在疾病发病机制中发挥作用。硫酸酯酶修饰因子（SUMF1）是结缔组织重塑中的关键修饰因子，我们之前已经表明该基因中的几个SNP与COPD相关。本研究的目的是调查SUMF1基因SNP与肺功能高级特征之间的关联。对有（n = 154）或无（n = 405）COPD的从不吸烟者、既往吸烟者和当前吸烟者进行SUMF1基因中21个SNP的基因分型，并进行肺活量测定、体容积描记法、肺一氧化碳弥散量（）测量和脉冲振荡法。四个SNP（rs793391、rs12634248、rs2819590和rs304092）在杂合变异等位基因时显示患COPD的比值比显著降低，同时1秒用力呼气量（FEV）和FEV/用力肺活量（FVC）比值降低，外周阻力和电抗受损。此外，rs3864051变异等位基因纯合个体与COPD、较低的FEV/FVC、FEV和，以及外周阻力和电抗受损有很强的关联。其他SNP（rs4685744、rs2819562、rs2819561和rs11915920）则与肺容积受损相关，在具有变异等位基因的个体中表现为较低的FVC、肺总量和肺泡容积。SUMF1基因中的几个SNP显示与COPD和肺功能受损相关。这些SUMF1基因变异可能导致肺组织细胞外基质中硫酸化平衡不足，从而促进COPD的发展。
