Impact of ITGA4 (Rs200000911) Polymorphism on Gene Expression and Clinical Behavior in Chronic Lymphocytic Leukemia

Background: Single Nucleotide Polymorphisms (SNPs) are crucial biomarkers in hematological malignancies, influencing disease susceptibility, progression, and treatment response. The Integrin Alpha 4 (ITGA4) gene, encoding the α4 integrin subunit, is critical for lymphocyte homing and adhesion and is a therapeutic target.
Objective: This study aimed to investigate the ITGA4 polymorphism (rs200000911) and its gene expression profile in Chronic Lymphocytic Leukemia (CLL) patients. Patients and Methods: A case-control study was conducted with newly diagnosed CLL patients and matched controls. Genomic DNA was extracted from peripheral blood, and the rs200000911 locus was amplified via polymerase chain reaction (PCR) and sequenced using the Sanger method. ITGA4 gene expression was quantified using quantitative real-time polymerase chain reaction
(qRT-PCR). Clinical parameters and laboratory findings were correlated with genetic data.
Results: The heterozygous TA genotype of rs200000911 was significantly more frequent among CLL patients than controls (45.9% vs. 13.5%, p < 0.01) and was associated with a higher risk of CLL (Odds Ratio; OR = 2.22, 95% CI: 1.26–3.91). CLL patients exhibited markedly elevated ITGA4 expression levels compared with controls (p < 0.001). Among CLL cases, the TA genotype correlated with adverse clinical features, including splenomegaly, lymphadenopathy, elevated lactate dehydrogenase (LDH), and increased β2-microglobulin (β2M) levels. Moreover, upregulated ITGA4 expression was linked to shorter time to first treatment (TTFT) and features of active disease.
Conclusion: The ITGA4 rs200000911 polymorphism and its associated gene expression pattern may contribute to CLL susceptibility and aggressiveness. The TA genotype appears to confer a higher risk and more active disease profile, supporting its potential as a prognostic biomarker. Further multicenter studies with larger cohorts are warranted to validate these findings and explore their translational implications in CLL management.