Glapa-Nowak Aleksandra, Szczepanik Mariusz, Banaszkiewicz Aleksandra, Iwańczak Barbara, Kwiecień Jarosław, Szaflarska-Popławska Anna, Grzybowska-Chlebowczyk Urszula, Osiecki Marcin, Kierkuś Jarosław, Banasiuk Marcin, Banasiewicz Tomasz, Madsen Jens, Walkowiak Jarosław
Department of Pediatric Gastroenterology and Metabolic Diseases, Poznań University of Medical Sciences, 60-572 Poznan, Poland.
Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, 02-091 Warszawa, Poland.
Children (Basel). 2021 Oct 21;8(11):946. doi: 10.3390/children8110946.
Deleted in malignant brain tumours 1 protein (DMBT1) and surfactant protein D (SFTPD) are antimicrobial peptides previously linked to inflammatory bowel disease (IBD) susceptibility. This study attempts to link the most potential IBD-associated polymorphisms in DMBT1 and SFTPD with the disease severity in children. A total of 406 IBD patients (Crohn's disease (CD) = 214 and ulcerative colitis (UC) = 192) were genotyped using hydrolysis probe assay. Clinical expression was described by disease activity scales, albumin and C-reactive protein levels, localisation and behaviour (Paris classification), systemic steroid, immunosuppressive, biological, and surgical treatment, number of exacerbation-caused hospitalisations, relapses and nutritional status. IBD patients with the risk genotype (AA) in DMBT1 rs2981804 had more frequent biological treatment (AA: vs. AG/GG; = 0.012), concomitant diseases (AA vs. AG vs. GG; = 0.015) and cutaneous manifestations (AA vs. AG/GG, = 0.008). In UC, rs2981804 genotypes might be linked with albumin concentrations at diagnosis (AA vs. AG vs. GG; = 0.009). In CD, DMBT1 rs2981745 was significantly associated with the number of severe relapses per year of disease ( = 0.020) and time-to-immunosuppression ( = 0.045). SFTPD was seemingly found to be associated with age at first immunosuppression in IBD (CC vs. CT vs. TT; = 0.048). In conclusion, selected polymorphisms of DMBT1 and SFTPD might be associated with some disease severity measures in children with IBD. However, the magnitude of associations and their clinical relevance might be minor.
恶性脑肿瘤缺失蛋白1（DMBT1）和表面活性蛋白D（SFTPD）是先前与炎症性肠病（IBD）易感性相关的抗菌肽。本研究试图将DMBT1和SFTPD中最具潜在IBD相关性的多态性与儿童疾病严重程度联系起来。使用水解探针分析法对总共406例IBD患者（克罗恩病（CD）=214例，溃疡性结肠炎（UC）=192例）进行基因分型。通过疾病活动量表、白蛋白和C反应蛋白水平、定位和行为（巴黎分类法）、全身类固醇、免疫抑制、生物和手术治疗、因病情加重导致的住院次数、复发情况和营养状况来描述临床表型。DMBT1 rs2981804具有风险基因型（AA）的IBD患者接受生物治疗的频率更高（AA：与AG/GG相比；P=0.012），合并症更多（AA与AG与GG相比；P=0.015），皮肤表现更多（AA与AG/GG相比，P=0.008）。在UC中，rs2981804基因型可能与诊断时的白蛋白浓度有关（AA与AG与GG相比；P=0.009）。在CD中，DMBT1 rs2981745与疾病每年严重复发的次数（P=0.020）和开始免疫抑制的时间（P=）显著相关。SFTPD似乎与IBD首次免疫抑制的年龄有关（CC与CT与TT相比；P=0.048）。总之，DMBT1和SFTPD的特定多态性可能与IBD儿童的某些疾病严重程度指标有关。然而，关联的程度及其临床相关性可能较小。
