Association of the CCL2 A/G (rs3760399) gene variant and its expression with COPD risk and response to combined budesonide/formoterol therapy

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and heterogeneous responses to inhaled therapy. CCL2 has been implicated in chronic inflammation and may contribute to corticosteroid non-responsiveness. This study investigated the association of the CCL2 A/G (rs3760399) gene variant and its expression with COPD risk and budesonide/formoterol (B/F) treatment response. A case-control study was performed with 150 COPD patients and 150 healthy controls. Genotyping was performed using the PCR-RFLP method, and qPCR was used to measure CCL2 gene expression. Multivariate logistic regression analysis was done to predict treatment response. Statistical analysis was done using GraphPad (Ver.8.0) and SPSS (Ver. 20). It was found that the “GG” genotype was significantly more prevalent in COPD patients than healthy controls (p = 0.0033; OR = 3.929). CCL2 gene expression was markedly elevated in COPD patients (p < 0.0001), with individuals carrying the “GG” genotype exhibiting higher expression levels than those with “AA” (p = 0.0009) or “AG” (p = 0.0368) genotypes. However, no significant association was found between the CCL2 variant and the responder versus non-responder groups, although higher CCL2 expression was observed in non-responders (p = 0.0041). Logistic regression analysis identified elevated CCL2 expression as an independent predictor of B/F non-responsiveness (p = 0.031; OR = 4.956). These findings indicate that the CCL2 (rs3760399) variant and elevated expression are linked to COPD risk, while higher CCL2 expression may predict non-response to B/F therapy.