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Int J Med Sci 2014; 11(4):365-372. doi:10.7150/ijms.7696 This issue Cite

Research Paper

Decreased Activities of Apolipoprotein M Promoter Are Associated with the Susceptibility to Coronary Artery Diseases

Lu Zheng¹, Guanghua Luo¹, Jun Zhang¹, Qinfeng Mu¹, Yuanping Shi¹, Maria Berggren-Söderlund², Peter Nilsson-Ehle², Xiaoying Zhang^1✉, Ning Xu^{2 ✉}

1. Comprehensive Laboratory, Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
2. Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, S-221 85 Lund, Sweden.

✉ Corresponding author: Ning Xu, Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, S-221 85 Lund, Sweden, Phone: (46)736395462: e-mail address: ning.xulu.se or Xiaoying Zhang, Comprehensive Laboratory, Third Affiliated Hospital of Soochow University, Changzhou 213003, China. Phone: (86)519-68871278; e-mail address: zhangxy6689996com More

Abstract

The present study investigated the correlation among genetic polymorphisms of the proximal promoter region of apolipoprotein M (apoM) gene, the polymorphisms in relation to apoM expressions and the susceptibility to coronary artery diseases (CAD) in a Han Chinese population. Four common polymorphic sites, i.e., T-1628G, C-1065A, T-855C and T-778C, were confirmed, and a new deletion mutation C-724del was found, in 206 CAD patients and 209 non-CAD patients using direct DNA sequencing analyses. Occurrences of alleles T-1628G, T-855C and C-724del were significantly higher in CAD patients compared to non-CAD patients. Moreover we examined all these polymorphisms in relation to apoM expression by applying luciferase reporter assay. It demonstrated that constructs -855C and 724del showed obvious decreased luciferase activities, i.e., (0.93±0.15 vs. 2.11±0.15; P=0.012) and (1.13±0.25 vs. 2.11±0.15; P=0.009) respectively, which indicates these two polymorphisms could confer decreased apoM expressions. Meanwhile the occurrences of these two SNP were also significantly higher in the CAD patients than in non-CAD patients. It is therefore reasonable to speculate that down-regulated apoM expressions in relation to these polymorphisms may affect HDL and cholesterol metabolism in vivo and further influence the susceptibility to CAD, although the underlying mechanisms need further investigation.

Keywords: apolipoprotein M, promoter, polymorphism, expression, coronary artery diseases

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