IL6 genetic variants haplotype is associated with susceptibility and disease activity but not with therapy response in patients with inflammatory bowel disease

• Published in: International journal of colorectal disease 2021-02, Vol.36 (2), p.383-393
• Main Authors: Gonçalves, Beatriz Piantoni, Flauzino, Tamires, Inoue, Cláudia Junko, de Paula, Jaqueline Costa Castardo, Galvão, Talita Cristina, de Alcantara, Camila Cataldi, Miyazaki, Paula Kikuchi, Rosa, Lucilene, Westmore, Silva, Lozovoy, Marcell Alysson Batisti, Reiche, Edna Maria Vissoci, Simão, Andréa Name Colado
• Format: Article
• Language: English
• Subjects: Adalimumab; Analysis; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - genetics; Crohn Disease - drug therapy; Crohn Disease - genetics; Crohn's disease; Disease; Disease susceptibility; Endoscopy; Gastroenterology; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; Genetic research; Genotypes; Haplotypes; Haplotypes - genetics; Hepatology; Humans; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - genetics; Interleukin 6; Interleukin-6 - genetics; Internal Medicine; Intestine; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Original Article; Polymorphism, Single Nucleotide - genetics; Proctology; Surgery; Tumor necrosis factor; Tumor necrosis factor-α; Ulcerative colitis
• ISSN: 0179-1958; 1432-1262
• DOI: 10.1007/s00384-020-03743-3

Purpose The aim of the present study was to evaluate the IL6 −174 G>C (rs1800795) and −572 G>C (rs1800796) genetic variants and their association with inflammatory bowel diseases (IBDs), disease activity, and response to TNF-α inhibitors. Methods The study included 178 patients with IBD and 224 healthy controls. Among the IBD patients, 66 of them were in use of TNF-α inhibitors therapy and were followed during 48 weeks and categorized as responders and non-responders. Results In total, 89 (50.0%) had ulcerative colitis (UC) and 89 (50.0%) had Crohn’s disease (CD). The IL6 −572 CC genotype presented a protective effect in CD patients in codominant and recessive models, while the IL6 −174 CC genotype was associated with susceptibility to UC and CD. The presence of G/C haplotype in the recessive model (GCGC) was associated with UC. The Crohn’s disease endoscopic index of severity was low in those patients carrying the GCGC haplotype. It was observed that there was no association between the IL6 genetic variants and TNF-α inhibitor therapy response. Conclusion The G/C haplotype (recessive model) was associated with susceptibility to UC but not to CD. However, the G/C haplotype (dominant model) was associated with the endoscopic activity of CD. Moreover, these IL6 variants did not predict the TNF-α inhibitor therapy response.