ADGRE2 Gene Polymorphism and Its Influence on CML Pathogenesis

Abstract

Chronic myeloid leukemia (CML) is a type of blood cancer that begins in the hematopoietic stem cell (HSC) compartment. It is characterized by a specific chromosomal aberration known as the Philadelphia (Ph) chromosome, which arises from a reciprocal translocation between chromosomes 9 and 22, leading to the union of the BCR and ABL1 genes. While the fusion gene is a major contributor to CML, several other genes are also implicated in the disease's progression. Until recently, little research had been conducted to identify single nucleotide polymorphisms (SNPs) associated with CML. Therefore, this study aims to investigate the influence of missense variants on the structure and function of the ADGRE2 gene and to identify missense variants associated with CML and its clinical and pathological characteristics. Missense variants of ADGRE2 were retrieved from the ENSEMBL genome browser, and the pathogenicity of deleterious variants was assessed using six different consensus tools. Additionally, various in silico tools were employed to explore the relationship between damaging SNPs, function, stability, and structure. Genotype analysis was performed on collected blood samples, revealing that the most pathogenic SNP among all missense variants was rs765071211 (D67N). Significant differences were observed between the wild-type and mutant variant (D67N) structures of ADGRE2. Genotype analysis indicated an association between the variant and CML, as genotypes CT and TT were found to have significant P-values. Genotype heterozygous CT has been identified as a risk factor for CML, while TT has a protective role in CML patients. This study suggests that the ADGRE2 SNP rs765071211 could serve as a potential genetic marker for the diagnosis of CML.