Is a rare CXCL8 gene variant a new possible cause or curse factor of inflammatory bowel disease?

Marcin Gabryel ¹ Oliwia Zakerska-Banaszak ² Karolina Ladziak ² Katarzyna Anna Hubert ² Alina Baturo ¹ Joanna Suszynska-Zajczyk ³ Magdalena Hryhorowicz ³ Agnieszka Dobrowolska ¹ Marzena Skrzypczak-Zielinska ^2*

• ¹ Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
• ² Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland
• ³ Department of Biochemistry and Biotechnology, Faculty of Agronomy and Bioengineerring, Poznan University of Life Sciences, Poznan, Poland

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 CXCL8 gene, assumes a crucial chemotactic role in leukocyte migration. This study aimed to investigate whether an association exists between IBD, and two CXCL8 variants: c.-251A>T (rs4073) and c.91G>T (rs188378669), as well as IL-8 concentration.We analyzed the distribution of both variants among 353 Polish IBD patients and 200 population subjects. The c.91T stop-gained allele was significantly more frequent in IBD patients (2.12%) than in controls (0.25%) (p = 0.0121), while the c.-251T allele frequencies were similar (54% vs. 51.5%, p = 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 pg/ml vs. 51.5 pg/ml, p<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.The findings suggest that the CXCL8 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.