CXCL12 rs1801157 Polymorphism Is Associated with Antiatherogenic Lipoprotein Subfraction Profile Independent of Coronary Artery Disease Risk in a Turkish Population: A Case–Control Study

Background/Objectives: Cardiovascular diseases remain a leading cause of global mortality. The C-X-C motif chemokine ligand 12 (CXCL12) gene has been implicated in atherosclerosis; however, its relationship with lipoprotein subfraction profiles remains unclear. The primary objective of this study was to investigate the association between the CXCL12 rs1801157 C>T single nucleotide polymorphism (SNP) and coronary artery disease (CAD) risk in a Turkish population. The secondary objective was to evaluate the relationship between this polymorphism and LDL and HDL lipoprotein subfraction profiles. Methods: This case–control study included 139 patients with angiographically confirmed CAD and 125 healthy controls. Genotyping was performed using TaqMan real-time polymerase chain reaction (PCR). Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were analyzed using the Lipoprint® polyacrylamide gel electrophoresis system. Multivariable logistic and linear regression analyses were performed, adjusting for age, sex, body mass index (BMI), and major cardiovascular risk factors. Results: No significant differences in rs1801157 genotype or allele distributions were observed between groups (overall χ2 = 0.459, p = 0.796). Logistic regression confirmed that the polymorphism was not an independent predictor of CAD risk (CT: OR = 1.396, p = 0.409; TT: OR = 1.458, p = 0.694). HDL-C was an independent protective factor (OR = 0.952, 95% CI: 0.910–0.996; p = 0.029). Notably, TT homozygous carriers exhibited significantly higher large HDL (p = 0.018) and intermediate HDL (p < 0.001) subfraction levels and markedly lower small LDL concentrations (p < 0.001). Multivariable linear regression confirmed these associations were independent of age, sex, and BMI. Conclusions: The CXCL12 rs1801157 variant does not directly influence CAD susceptibility but modulates lipoprotein quality by promoting larger HDL subfractions and reducing atherogenic small LDL particles, suggesting an indirect cardioprotective role through lipid metabolism.