Allelic, Genotypic, and Haplotypic Analysis of Cytokine IL17A, IL17F, and Toll-like Receptor TLR4 Gene Polymorphisms in Metabolic-Dysfunction-Associated Steatotic Liver Disease: Insights from an Exploratory Study

(1) Background: Interleukin 17 (IL17) and toll-like receptor 4 (TLR4) elevate the risk of metabolic and liver diseases. (2) Methods: This study's objective was to explore the association of IL17 and TLR4 gene polymorphisms with MASLD susceptibility and test their effect on serum IL17 and TLR4 levels. A total of 43 patients with MASLD (MASH/MAFL) and 38 healthy individuals were genotyped for IL17F-<i>A7488G</i>, IL17A-<i>G197A</i>, TLR4-<i>Asp299Gly</i>, and TLR4-<i>Thr399Ile</i> polymorphisms using PCR-RFLP. ELISA methods determined IL17F, IL17A, and TLR4 serum levels. (3) Conclusions: Patients carrying the variant genotypes (<i>A/G + G/G</i>) of IL17-<i>A7448G</i> (OR = 5.25), (<i>G/A + A/A</i>) of <i>IL17-G197A</i> (OR = 10.57), (<i>Asp/Gly + Gly/Gly</i>) of TLR4-<i>Asp299Gly</i> (OR = 3.52), or (<i>Thr/Ile + Ile/Ile</i>) of TLR4-<i>Thr399Ile</i> (OR = 9.87) had significantly increased odds of MASH. Genotype (<i>G/A + A/A</i>) of IL17-<i>G197A</i> was significantly associated with the odds of MAFL (<i>p</i> = 0.0166). Allele <i>A</i> of the <i>IL17-G197A</i> polymorphism was significantly related to increased odds of MAFL (OR = 4.13, <i>p</i> = 0.0133). In contrast, allele <i>A</i> of IL17-<i>G197A</i> (OR = 5.41, <i>p</i> = 0.008), allele <i>Gly</i> of TLR4-<i>Asp299Gly</i> (OR = 3.19, <i>p</i> = 0.046), and allele <i>Ile</i> of TLR4-<i>Thr399Ile</i> (OR = 6.94, <i>p</i> = 0.008) polymorphisms were significantly related to an increased risk of MASH. Allele <i>A</i> of IL17A-<i>G197A</i>, allele <i>Gly</i> of TLR4-<i>Asp299Gly</i>, and allele <i>Ile</i> of TLR4-<i>Thr399Ile</i> gene polymorphisms were significantly associated with the increased odds of MASLD. In patients with MASLD, we found significant influence from the IL17A-<i>G197A</i> gene polymorphism on IL17F levels (<i>p</i> = 0.0343).