Zakerska-Banaszak Oliwia, Gozdzik-Spychalska Joanna, Gabryel Marcin, Zuraszek Joanna, Skrzypczak-Zielinska Marzena, Slomski Ryszard, Dobrowolska Agnieszka, Piorunek Tomasz, Batura-Gabryel Halina
Institute of Human Genetics Polish Academy of Sciences, Poznan, Poland.
Department of Pulmonology, Allergology and Lung Oncology, Poznan University of Medical Sciences, Poznań, Poland.
F1000Res. 2022 Nov 22;11:379. doi: 10.12688/f1000research.110472.3. eCollection 2022.
The main aim of this study was to evaluate whether selected polymorphic variants in genes from the inflammatory pathway can be predictors of pulmonary or digestive manifestation of cystic fibrosis, as well as of severity of lung disease. Using pyrosequencing and sequencing we have genotyped 12 variants in (rs361525, rs1800629), (rs4073, rs2227306, rs2227307, rs188378669), (rs16944, rs1143634, rs1142639, rs1143627), (rs1800795) and (rs1800896) genes in a cohort of 55 Polish patients with diagnosed cystic fibrosis and controls. In our study group, a pulmonary manifestation of disease revealed 44 of subjects (80%), and digestive symptoms dominated in 11 (20%) of analyzed individuals. Severe lung dysfunction has occurred in 20 (36.4%) of patients. We proved, that two promoter variants of rs1143627 (c.-118G > A) and rs16944 (c.-598T > C) are presented significantly more often in patients with severe character of lung disease compared to mild (82.5% 62.8%, p-value 0.030, and 87.5% 64.3%, p-value 0.008, respectively) in cystic fibrosis course. Haplotype AC formed by both changes had also a higher frequency (80%) in patients with severe course compared to the mild character (61.4%) of disease. However, the frequency of promoter variant c.-308C > T (rs1800629) was presented at a significantly lower level in the patient's group compared to healthy controls (2.7% 15%, p-value 0.001). Furthermore, the presence of methicillin-resistant significantly correlated with the lower FEV1% in patients (p-value 0.01). Genetic variants, rs1143627 and rs16944, of are promising candidates as predictors of the severe character of lung disease in Polish patients with cystic fibrosis.
本研究的主要目的是评估炎性途径相关基因中选定的多态性变体是否可作为囊性纤维化肺部或消化系统表现以及肺部疾病严重程度的预测指标。我们采用焦磷酸测序和测序技术，对55名确诊为囊性纤维化的波兰患者及对照人群的（rs361525、rs1800629）、（rs4073、rs2227306、rs2227307、rs188378669）、（rs16944、rs1143634、rs1142639、rs1143627）、（rs1800795）和（rs1800896）基因中的12个变体进行了基因分型。在我们的研究组中，44名受试者（80%）出现了肺部疾病表现，11名（20%）分析个体以消化系统症状为主。20名患者（36.4%）出现了严重的肺功能障碍。我们证明，在囊性纤维化病程中，rs1143627（c.-118G>A）和rs16944（c.-598T>C）这两个启动子变体在严重肺部疾病患者中的出现频率明显高于轻度患者（分别为82.5%对62.8%，p值0.030；87.5%对64.3%，p值0.008）。由这两种变化形成的单倍型AC在疾病严重病程患者中的频率（80%）也高于轻度病程患者（61.4%）。然而，启动子变体c.-308C>T（rs1800629）在患者组中的出现频率明显低于健康对照组（2.7%对15%，p值0.001）。此外，耐甲氧西林的存在与患者较低的FEV1%显著相关（p值0.01）。基因变体rs1143627和rs16944有望成为波兰囊性纤维化患者肺部疾病严重程度的预测指标。
