Assessing Candidate Genetic Variants Associated with Ulcerative Colitis (UC): A Case-Control Study

Background & Objectives: This study explored the immunogenetic perspective underpinning the susceptibility and progression of ulcerative colitis (UC), a form of inflammatory bowel disease (IBD) characterized by chronic auto-inflammatory processes in the gut. This multifactorial disorder occurs in genetically predisposed individuals experiencing dysbiosis, wherein genetic factors contribute to intestinal imbalance and modulate immune pathways. Recent discoveries of novel genetic loci and polymorphisms have highlighted racial diversity in IBD susceptibility. Our research addresses a gap in the literature by examining the association between specific genetic loci and UC susceptibility in a defined ethnic group, aiming to identify and evaluate candidate genetic polymorphisms as part of an immunogenetic assessment to elucidate the mechanisms underlying UC susceptibility and progression. Materials & Methods: In this case-control study, we evaluated 794 reference sequences (rs) from global, national, and regional ethnic databases, which were utilized for genotyping 150 control subjects via blood samples. We selected and investigated five genetic variants—rs3764147 (LACC1 or C13orf31), rs763780 (IL17F), rs3749171 (GPR35), rs1260326 (GCKR), and rs4077515 (CARD9)—using Amplification-refractory mutation system polymerase chain reaction (ARMs PCR) followed by Sanger sequencing for confirmation in 50 UC patients. Results: Analysis of the candidate genetic polymorphisms revealed that the LACC1, IL17F, and GPR35 variants were significantly associated with UC, with the primary outcome focusing on this association and the secondary outcome examining the allelic frequencies of the five variants in both groups. Conclusion: Ultimately, our findings demonstrate that the GPR35 (G protein-coupled receptor 35) rs3749171, IL17F (Interleukin 17F) rs763780, and LACC1 (laccase domain containing 1) rs3764147 variants contribute to UC susceptibility as a polygenic trait in the studied ethnic group. This underscores the potential importance of genetic architecture across different ethnicities, offering valuable biological insights into IBD pathogenesis and guiding future research.

Assessing Candidate Genetic Variants Associated with Ulcerative Colitis (UC): A Case-Control Study Keywords:

Ulcerative colitis , LACC1 , IL17F , GPR35 , CARD9 , Single Nucleotide Polymorphism (SNP)