Analyse préliminaire du polymorphismeR381Q du gène IL23R dans la Leucémie Myéloïde Aiguë dans un échantillon de la population l’Ouest Algérien : étude cas –témoins et investigation bio-informatique

Abstract

Acute Myeloid Leukemia (AML) represents one of the most complex challenges in modern oncology, characterized by a malignant proliferation of myeloid progenitors. Beyond environmental factors, genetic susceptibility, notably through single nucleotide polymorphisms (SNPs), plays a role in the pathogenesis of this disease. The main objective of this work is to evaluate the association between the R381Q (rs11209026) genetic variant of the $IL23R$ gene and the risk of occurrence of AML in a sample of the Western Algerian population. The experimental approach involved a total of 85 individuals, divided into 43 patients with acute myeloid leukemia (AML) and 42 healthy controls. This study combined a molecular approach based on the genotyping of the R381Q (rs11209026) polymorphism of the IL23R gene by real-time PCR (TaqMan PCR), a statistical analysis performed using SPSS software (version 21) to assess the association between this polymorphism and susceptibility to AML, as well as a bioinformatic (in silico) study designed to predict the structural impact of the amino acid substitution induced by this SNP on the IL-23R receptor. Our results highlight a highly significant genotypic association between the rs11209026 polymorphism and AML in our study population, with AG versus AA (OR = 8.64 [1.71–43.67]; p = 0.006), as well as the dominant model (AG+GG versus AA) (OR = 7.27 [1.49–35.39]; p = 0.003). Furthermore, the bioinformatic analysis carried out via Ensembl VEP, PolyPhen-2 tools, and structural modeling by AlphaFold confirms that this R381Q amino acid substitution has a direct structural impact on the IL-23R receptor molecule. This potential alteration is likely to modulate the signaling of the IL-23/IL-23R pathway and influence certain immune mechanisms involved in the pathogenesis of AML. This work constitutes an essential preliminary step that opens up new perspectives for the exploration of other genetic biomarkers.