title: Association of Increased Serum Sema3E with TRIB3 Q84R Polymorphism and Carotid Atherosclerosis in Metabolic Syndrome.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University, Ji'nan, China.|Department of Geriatrics, Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Ran-Ran
authors.initials: RR
authors.lastname: Qin
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Song
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Li
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Ming-Hao
authors.initials: MH
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology Qilu Hospital of Shandong University, Ji'nan, China wangzhihaosdu@126.com.|Department of Geriatrics, Qilu Hospital of Shandong University, Ji'nan, China.
authors.forename: Zhi-Hao
authors.initials: ZH
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D002340:Carotid Artery Diseases / Q000097:blood* / Q000150:complications / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D039961:Semaphorins / Q000097:blood*
chemical_list: D018797:Cell Cycle Proteins; D012097:Repressor Proteins; C494123:SEMA3E protein, human; D039961:Semaphorins; C474831:TRIB3 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Semaphorin 3E; Tribbles 3; carotid atherosclerosis; metabolic syndrome