title: Correlation analysis between ApoM gene-promoter polymorphisms and coronary heart disease.
abstract: OBJECTIVE
  Apolipoprotein M (ApoM), a 25-kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with high-density lipoprotein cholesterol (HDL-C). Studies have suggested ApoM to be important for the formation of pre-β-HDL and to increase cholesterol efflux from macrophage foam cells. The aim of this study was to explore the association of single-nucleotide polymorphisms (SNPs) in the ApoM promoter with coronary atherosclerotic disease (CAD), and the contribution of latent factors.
  
  
  METHODS
  ApoM was measured in samples from two separate case-control studies, of whom 88 patients developed CAD and 88 were controls. Whole-blood samples from subjects were genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP). Luciferase activities were measured for HepG2 cells with two SNPs, rs805296 (T-778C) and rs940494 (T-855C), and after interfering with or overexpressing the predicted transcription factors. The ability of the SNPs to combine with nucleoproteins was analysed by electrophoretic mobility shift assay (EMSA).
  
  
  RESULTS
  Mean plasma ApoM concentrations in the CAD and non-CAD groups were 9.58 ± 4.30 and 12.22 ± 6.59 µg/ ml, respectively. Correlation studies of ApoM concentrations with several analytes showed a marked positive correlation with HDL-C, fasting plasma glucose and triglyceride levels. The CC genotype showed lower luciferase activities compared to the TC and TT genotypes. The ApoM-855 mutant-type could bind to the AP-2α. Interference and overexpression of AP-2 increased and decreased luciferase activities of the wild and mutant types to different degrees.
  
  
  CONCLUSIONS
  ApoM may be a biomarker of CAD. ApoM-855 T→C substitution provides binding sites for AP-2α and reduces ApoM transcription activity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Wan Nan Medical College, Anhui 241000, China. Email: zhangyao@ahedu.gov.cn.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Clinical Testing and Diagnosis, Experimental Centre of Bengbu Medical College, Anhui 233000, China.
authors.forename: Li-Zhu
authors.initials: LZ
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, Beng Bu Medical College, Anhui 233000, China.
authors.forename: Qing-Ling
authors.initials: QL
authors.lastname: Yang
authors.affiliation: Clinical Testing and Diagnosis, Experimental Centre of Bengbu Medical College, Anhui 233000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Centre for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan, Peoples' Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000368:Aged; D001053:Apolipoproteins / Q000097:blood / Q000235:genetics*; D000075243:Apolipoproteins M; D001665:Binding Sites; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D017930:Genes, Reporter; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D056945:Hep G2 Cells; D006801:Humans; D054834:Lipocalins / Q000097:blood / Q000235:genetics*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009698:Nucleoproteins / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012307:Risk Factors; D050656:Transcription Factor AP-2 / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C400523:APOM protein, human; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D005819:Genetic Markers; D054834:Lipocalins; D009698:Nucleoproteins; D050656:Transcription Factor AP-2; D008156:Luciferases