To investigate the impact of SNPs and haplotypes of antiplatelet drug metabolism-related genes on the risk of premature coronary artery disease (PCAD).
Approach:
Study Design: Real-world study enrolling 1,108 participants, including PCAD patients and controls without obstructive CAD.
Genotyping: Twelve SNP loci were genotyped using PCR amplification and digoxigenin-based colorimetric detection.
Data Analysis: Linkage disequilibrium and haplotype frequencies assessed using Haploview; GMDR method used for G × G and G × E interactions.
Statistical Methods: Logistic regression evaluated combined effects of SNPs and haplotypes.
Key Findings:
Significant differences in genotype and allele frequencies for rs12769205, rs3758580, rs4917623, and rs1330344 between PCAD patients and controls (P < 0.05).
The dominant model of rs12769205 showed a protective effect, while rs3758580, rs4917623, and rs1330344 were associated with increased PCAD risk.
Haplotype analysis indicated protective haplotypes (CYP2C19 G-C-C-A-A and G-C-C-C-C) and risk haplotypes (CYP2C19 G-C-A-A-A, PTGS1 C-A-A, etc.).
Higher annual oral corticosteroid exposure was associated with greater odds of systemic adverse events, with avascular bone necrosis and pneumonia showing dose-dependent associations with cumulative dose and osteoporosis associated with longer annual exposure duration.
