Genetic variant rs2243115 of the IL-12/IL-35 pathway contributes to the risk of coronary artery disease.

Abstract

Background: Coronary artery disease (CAD) involves inflammation. IL-12p35, a common subunit of both IL-12 and IL-35, is encoded by the IL12A gene and is a potential therapeutic target in CAD. We probed into the genetic relationships between IL12A and CAD in a Chinese Han population to provide a novel potential target and a theoretical basis for the anti-inflammatory therapies in CAD. Materials and Methods: In total, 768 patients with CADs and 768 controls were recruited for a case-control association analysis of the functional genetic variant rs2243115 of IL12A. Allelic and genotypic associations between rs2243115 and CAD and its subgroup were assessed by Logistic regression analysis. Additionally, multiple linear regression analysis was performed to explore the association between rs2243115, serum lipid levels and CAD severity. Bioinformatic tools were used to predict the potential function of rs2243115. Results: Our results showed no differences in the allele and genotype frequency distribution of rs2243115 between patients with CAD and controls. The subgroup analysis found no association between rs2243115 and CAD in either male or female groups. Furthermore, rs2243115 was not related to early- or late-onset CAD, or CAD severity. However, we did observe that rs2243115 was negatively related to HDL-c level (P=0.016, β =-0.063) and positively related to LDL-c level (P=0.029, β=0.058). Biological function prediction indicated many functional elements in the rs2243115 region, suggesting that rs2243115 may regulate gene expression in the IL-12/IL-35 pathway. Conclusion: The functional genetic variant, rs2243115, of IL12A, may play a role in CAD by regulating the IL-12/IL-35 pathway and affecting lipid levels and inflammatory responses, thereby providing a potential therapeutic target for CAD.