Interleukin-4 Gene Polymorphisms in Romanian Patients with Inflammatory Bowel Diseases: Association with Disease Risk and Clinical Features

Elena Mirela Ionescu; Andrei Ovidiu Olteanu; Cristian George Tieranu; Luis Ovidiu Popa; Silvia Ioana Andrei; Carmen Monica Preda; Monica Irina Dutescu; Mihai Bojinca; Ioana Tieranu; Olivia Mihaela Popa

doi:10.3390/diagnostics13081465

Interleukin-4 Gene Polymorphisms in Romanian Patients with Inflammatory Bowel Diseases: Association with Disease Risk and Clinical Features

Diagnostics (Basel). 2023 Apr 18;13(8):1465. doi: 10.3390/diagnostics13081465.

Authors

Affiliations

¹ Department of Gastroenterology, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.
² Department of Gastroenterology, "Elias" Emergency University Hospital, 011461 Bucharest, Romania.
³ Molecular Biology Department, "Grigore Antipa" National Museum of Natural History, 011341 Bucharest, Romania.
⁴ Clinic of Internal Medicine II, Thüringen-Kliniken "Georgius Agricola", 07318 Saalfeld, Germany.
⁵ "Prof. Dr. C. T. Nicolau" National Institute of Blood Transfusion, 011155 Bucharest, Romania.
⁶ Department of Rheumatology and Internal Medicine, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.
⁷ Department of Pediatrics, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.
⁸ Department of Immunology and Pathophysiology, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.

Abstract

1.

Introduction: Multiple cytokines have been studied for their role in the propagation of the inflammatory process related to inflammatory bowel diseases (IBD), but the role of interleukin-4 remains controversial. The aim of this study was to evaluate the role of two IL-4 gene single nucleotide polymorphisms (SNPs) in disease susceptibility and phenotypic expression. 2.

Materials and methods: A group of 160 patients with IBD (86CD/74UC) and 160 healthy controls were genotyped for IL-4 rs2243250/-590C/T and rs2070874/-34C/T using real-time polymerase chain reaction with TaqMan assay. 3.

Results: The analysis of IBD patients and controls revealed a significantly reduced frequency of the minor allele T of both SNPs in CD patients (p = 0.03, OR 0.55 and p = 0.02, OR 0.52) and for the entire IBD group (p = 0.01, OR 0.57 and p = 0.01, OR 0.55). Haplotype analysis identified the most frequent haplotype (rs2243250/rs2070874 CC) associated with a high risk for developing IBD (either UC or CD) (p = 0.003). IBD patients with extraintestinal manifestations had significantly increased frequency of the minor alleles T. We also found an association between the presence of allele C of rs2070874 and response to antiTNF treatment. 4.

Conclusions: This is the first study to investigate the IL-4 gene's relation to IBD susceptibility conducted in Romania. Both SNPs were found to be associated with disease susceptibility and phenotypic features, such as extraintestinal manifestations and response to antiTNF agents.

Keywords: crohn’s disease; inflammatory bowel disease; interleukin-4; single nucleotide polymorphism; ulcerative colitis.

Grants and funding

Publication of this paper was supported by the University of Medicine and Pharmacy “Carol Davila”, through the institutional program “Publish not Perish”.