Association of Increased Serum Sema3E with TRIB3 Q84R Polymorphism and Carotid Atherosclerosis in Metabolic Syndrome.

OBJECTIVES: Semaphorin-3E, provoking inflammation and insulin resistance which leads to metabolic syndrome, exerts obscure effects on carotid atherosclerosis in metabolic syndrome. The Tribbles 3 Q84R polymorphism is involved in insulin resistance. This study aims to investigate whether the Tribbles 3 Q84R polymorphism has profound effects on serum semaphorin 3E and what effect semaphorin 3E exerts on carotid atherosclerosis. METHOD: A total of 518 unrelated Chinese subjects consisted of control (n=258) and metabolic syndrome (n=260) groups. Clinical and biochemical characteristics were collected. The level of serum semaphorin 3E was measured by enzyme-linked immunosorbent assay. Genotyping of the functional Tribbles 3 Q84R polymorphism was achieved by RFLP-PCR method. All subjects underwent carotid ultrasonography to determine carotid intima-media thickness (considered atherosclerosis if above 0.9 mm). RESULTS: Serum semaphorin 3E was significantly increased in metabolic syndrome (P=0.012) as compared with the control group. Among the metabolic syndrome group, those with RR84 genotype had significantly higher levels of serum semaphorin 3E than those with QQ84 or QR84 genotypes (P=0.003, P=0.004) with similarity amongst the control group. Factorial analyses showed statistically significant interactions between RR84 genotype and metabolic syndrome (P=0.019 for interaction for semaphorin 3E). Semaphorin 3E correlated positively with homeostasis model assessment insulin resistance (r=0.263, P=0.009) and carotid intima-media thickness (r=0.215, P=0.031). On partial analyses, after controlling for confounding factors, semaphorin 3E was positively correlated with carotid intima-media thickness (P=0.004). CONCLUSION: Individuals with metabolic syndrome demonstrated further increased serum semaphorin 3E, especially those with Tribbles 3 RR84 genotype. Increased serum semaphorin 3E may in part exacerbate insulin resistance and carotid atherosclerosis.