Gabryel Marcin, Zakerska-Banaszak Oliwia, Ladziak Karolina, Hubert Katarzyna Anna, Baturo Alina, Suszynska-Zajczyk Joanna, Hryhorowicz Magdalena, Dobrowolska Agnieszka, Skrzypczak-Zielinska Marzena
Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland.
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Front Immunol. 2025 Mar 19;16:1562618. doi: 10.3389/fimmu.2025.1562618. eCollection 2025.
The pathogenesis of inflammatory bowel diseases (IBD) involves genetic, environmental, immunological, and microbial factors; however, it remains unclear. Pro-inflammatory interleukin 8 (IL-8), encoded by the gene, assumes a crucial chemotactic role in leukocyte migration.
This study aimed to investigate whether an association exists between IBD and two variants, namely, c.-251A>T (rs4073) and c.91G>T (rs188378669), and IL-8 concentration. We analyzed the distribution of both variants among 353 Polish IBD patients and 200 population subjects using pyrosequencing, competitive allele-specific PCR and Sanger sequencing.
The c.91T stop-gained allele was significantly more frequent in IBD patients (2.12%) than in controls (0.25%) ( = 0.0121), while the c.-251T allele frequencies were similar (54% vs. 51.5%, = 0.4955). Serum IL-8 concentrations, measured using ELISA, were higher in IBD patients with the c.91 GG genotype compared to healthy controls (mean, 70.02 vs. 51.5 pg/ml, <0.01) and patients with c.91 GT (mean, 61.73 pg/ml). Moreover, clinical data indicated that carriers of the c.91T variant need more often corticosteroids and surgical treatment of the disease than GG homozygous IBD patients.
This suggest that the c.91T allele may influence IBD manifestation and the course of the disorders in Polish patients, potentially serving as a novel target for future studies and therapeutic approaches.
炎症性肠病（IBD）的发病机制涉及遗传、环境、免疫和微生物因素；然而，其发病机制仍不清楚。由该基因编码的促炎性白细胞介素8（IL-8）在白细胞迁移中起关键的趋化作用。
本研究旨在调查IBD与两个基因变体，即c.-251A>T（rs4073）和c.91G>T（rs188378669）以及IL-8浓度之间是否存在关联。我们使用焦磷酸测序、竞争性等位基因特异性PCR和桑格测序分析了353名波兰IBD患者和200名正常人群中这两种变体的分布情况。
IBD患者中c.91T截短突变等位基因的频率（2.12%）显著高于对照组（0.25%）（P = 0.0121），而c.-251T等位基因频率相似（54%对51.5%，P = 0.4955）。与健康对照组（平均70.02对51.5 pg/ml，P<0.01）和c.91 GT基因型患者（平均61.73 pg/ml）相比，采用酶联免疫吸附测定法测得的IBD患者中c.91 GG基因型血清IL-8浓度更高。此外，临床数据表明，与c.91 GG纯合子IBD患者相比，c.91T变体携带者更常需要使用皮质类固醇和进行手术治疗。
这表明c.91T等位基因可能影响波兰患者IBD的表现和疾病进程，可能成为未来研究和治疗方法的新靶点。
