Precision medicine approach to coronary artery disease: Haptoglobin phenotype‑guided risk assessment

Haptoglobin (HP) polymorphisms influence antioxidant function and coronary artery disease (CAD) susceptibility, showing notable ethnic variations. Comprehensive studies examining both HP phenotypes and serum concentrations in Chinese populations are lacking. The present study investigated associations between HP parameters and CAD risk in a Chinese cohort. The hospital‑based study enrolled 230 patients with CAD, 83 angiography‑defined controls (stenosis ≤40%) and 192 healthy controls. Serum HP concentrations were quantified using an immunoturbidimetric method. HP genotypes were determined using reverse transcription‑quantitative PCR and polyacrylamide gel electrophoresis. Multivariate logistic regression analysis was used to identify CAD predictors and genotype‑stratified analyses assessed HP associations with cardiac function, such as left ventricular ejection fraction (LVEF) and disease severity, as indicated by effected vessel count. Patients with CAD showed higher Hp2‑2 genotype prevalence (54.8 vs. 41.1% in healthy controls; P<0.001) and elevated genotype‑specific serum HP concentrations (HP2‑2, 1.50±0.84 vs. 0.85±0.42 g/l; P<0.001) compared with healthy controls. Serum HP concentration, hypertension, triglyceride concentration and Hp2‑2 phenotype were independently associated with CAD risk, with high‑density lipoprotein‑cholesterol identified as a protective factor. Notably, Hp1‑1 carriers exhibited an inverse HP‑LVEF correlation (r=‑0.607; P=0.010), while Hp2‑2 showed a moderate correlation with cardiac function (r=‑0.249; P=0.013). A significant positive correlation with HP‑vessel count trend also emerged in Hp1‑1 patients (r=0.410, P=0.065). HP concentration was a potent CAD risk biomarker in the investigated populations, with clinical relevance modified by genotype. Hp1‑1 carriers demonstrate particularly strong associations between elevated HP levels and impaired cardiac function. Therefore, implementation of genotype‑stratified HP assessment may enhance CAD risk evaluation in precision medicine approaches.