Oriano Martina, Aliberti Stefano, Guerini Franca Rosa, Agliardi Cristina, Di Francesco Carlotta, Gelmini Alice, Terranova Leonardo, Zanzottera Milena, Marchisio Paola, Clerici Mario, Blasi Francesco
Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy.
Respiratory Unit and Adult Cystic Fibrosis Center, Internal Medicine Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Biomedicines. 2021 Oct 29;9(11):1573. doi: 10.3390/biomedicines9111573.
Vitamin D modulates immune responses and its deficiency has been observed in more than 60% of bronchiectasis patients. Vitamin D binding protein (DBP) is coded by the GC gene, is involved in the transport of vitamin D, and includes a number of isoforms based on single nucleotide polymorphisms (SNPs) in the coding region at rs7041 and rs4855. We evaluated the possible clinical impact of DBP polymorphisms and isoforms in an observational, cross-sectional study conducted in 116 bronchiectasis patients, who were genetically characterized for rs4588 and rs7041 SNPs. Results showed that the GC1f isoform (rs7041/rs4588 A/G) correlated with a more severe disease (18.9% vs. 6.3%, = 0.038), a higher incidence of chronic infections (63.6% vs. 42%, = 0.041), and a lower BACI score (0.0 (0.0, 2.5) vs. 3.0 (0.0, 3.0), = 0.035). Moreover, blood concentration of vitamin D was higher in patients carrying GC1s (median (IQR): 20.5 (14.3, 29.7 vs. 15.8 (7.6, 22.4), = 0.037)). Patients carrying GC1f isoform have a more severe disease, more chronic infections and lower asthmatic comorbidity in comparison to those without the GC1f isoform. Presence of the GC1s isoform (rs7041/rs4588 C/G) seems to be associated to a milder clinical phenotype with increased vitamin D levels and lower comorbidities score.
维生素D可调节免疫反应，且在超过60%的支气管扩张症患者中观察到维生素D缺乏。维生素D结合蛋白（DBP）由GC基因编码，参与维生素D的转运，并基于rs7041和rs4855编码区域的单核苷酸多态性（SNP）包含多种亚型。我们在一项针对116例支气管扩张症患者的观察性横断面研究中评估了DBP多态性和亚型可能产生的临床影响，这些患者针对rs4588和rs7041 SNP进行了基因特征分析。结果显示，GC1f亚型（rs7041/rs4588 A/G）与更严重的疾病相关（18.9%对6.3%，P = 0.038）、慢性感染的更高发病率（63.6%对42%，P = 0.041）以及更低的BACI评分（0.0（0.0，2.5）对3.0（0.0，3.0），P = 0.035）。此外，携带GC1s的患者血液中维生素D浓度更高（中位数（四分位间距）：20.5（14.3，29.7）对15.8（7.6，22.4），P = 0.037）。与没有GC1f亚型的患者相比，携带GC1f亚型的患者疾病更严重、慢性感染更多且哮喘合并症更少。GC1s亚型（rs7041/rs4588 C/G）的存在似乎与更轻的临床表型相关，维生素D水平升高且合并症评分更低。
