The effect of inflammatory factors on unstable angina risk, from the gene level

Inflammation and its genetic regulation play crucial roles in the development of unstable angina (UA), a key manifestation of coronary artery disease (CAD). However, the genetic determinants that influence cytokine production and interindividual inflammatory responses remain incompletely understood, particularly in the Chinese population. This study aimed to clarify the relationship between inflammatory cytokine gene polymorphisms, serum cytokine expression, and UA risk. A hospital-based case-control study was conducted in 160 patients with UA and 280 age- and sex-matched healthy controls. Participants meeting the 2007 ACC/AHA UA/NSTEMI diagnostic criteria and angiographic evidence of ≥ 50% coronary stenosis were included, while individuals with systemic inflammatory or metabolic disorders were excluded. Serum cytokine levels (IL-1β, IL-6, IL-10, IL-17, IFN-γ, TNF-α) were quantified by ELISA, and 13 cytokine gene loci were genotyped using PCR-RFLP. Associations between polymorphisms and UA were evaluated using multivariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs). All cytokines were significantly elevated in UA patients compared with controls (p < 0.01), with IL-10 showing the largest increase (3.2-fold). Polymorphisms at seven loci were significantly associated with UA susceptibility: IL-1β - 511 C/T (TT vs. CC: OR = 6.39, 95% CI 2.94-13.87), TNF-α - 308 G/A (AA vs. GG: OR = 2.56, 95% CI 1.50-4.37), IL-6 - 1363 G/T (GT vs. GG: OR = 0.52, 95% CI 0.34-0.80), IL-10 - 1082 G/A and - 592 C/A, IL-17 rs2275913, and IFN-γ + 874 A/T (all p < 0.05). ROC analysis revealed strong discriminatory ability for IL-1β - 511 C/T (AUC = 0.87) and TNF-α - 308 G/A (AUC = 0.84), both with sensitivity and specificity > 80%. Moreover, carriers of risk alleles (e.g., IL-1β T, TNF-α A) exhibited higher cytokine levels, indicating functional upregulation of inflammatory activity. Cytokine gene polymorphisms, particularly IL-1β - 511 C/T and TNF-α - 308 G/A, are associated with heightened inflammatory responses and increased UA susceptibility. These variants may serve as potential genetic biomarkers for coronary instability, though further multicenter and functional validation is warranted before clinical application. ‌Keywords‌: unstable angina; coronary artery disease; inflammatory cytokines; genetic polymorphism; biomarker; Enzyme-Linked Immunosorbent Assay; Polymerase Chain Reaction-Restriction Fragment Length Polymorphism.