Polymorphisms in SOCS 1 and 3 and human coronary artery disease

Atherosclerosis is a multifactorial disease that is characterized by chronic inflammation at every stage, from initiation to progression, and eventually plaque rupture. Suppressors of cytokine signaling (SOCS) are a family of intracellular proteins playing a role in the physiological regulation of hormone and cytokine-mediated homeostasis. The SOCS proteins prevent excessive immune activation by negatively regulating the Jak/STAT pathways. We hypothesized that polymorphisms in SOCS 1 and 3 may differently affect the negative feedback loop and hence influence the degree of immune activation and the course of coronary artery disease (CAD). We screened the SOCS1 and the SOCS3 genes for polymorphisms and investigated the association of 7 polymorphisms each with angiographically documented CAD in a case control study (n=496). None of the polymorphisms was significantly associated with CAD but rs33977706 in SOCS1 and rs7207782 in SOCS3 showed borderline associations with CAD using an additive genetic model. In addition, rs33977706 in SOCS1 was associated with hsCRP levels in controls, suggesting that rs33977706 in SOCS1 may increase the inflammatory tone and accelerate CAD in humans.