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Decreased activities of apolipoprotein m promoter are associated with the susceptibility to coronary artery diseases.

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.

SUBMITTER: Zheng L

PROVIDER: S-EPMC3936031 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Decreased activities of apolipoprotein m promoter are associated with the susceptibility to coronary artery diseases.

Zheng Lu L Luo Guanghua G Zhang Jun J Mu Qinfeng Q Shi Yuanping Y Berggren-Söderlund Maria M Nilsson-Ehle Peter P Zhang Xiaoying X Xu Ning N

International journal of medical sciences 20140220 4

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. Occ ...[more]

PMID: 24578614

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Project description:BACKGROUND: It has been reported that rs940494 and rs805296 SNPs of apolipoprotein M (apoM) gene may confer the risk in the development of type 2 diabetes (T2D) and coronary artery disease (CAD) in the Han Chinese. However, a recent study demonstrated that rs805297 polymorphism is significantly associated with reduced total high density lipoprotein (HDL) levels in rheumatoid arthritis patients. But the relationship between rs805297 SNP and CAD has not been explored. The aim of the present study was to elucidate whether the rs805297 mutant allele is implicated in CAD and links to changes in blood lipid levels in these patients. METHODS: Three hundred CAD patients and three hundred and twelve non-CAD patients were subjected in the present study. All subjects were confirmed by the angiography. Plasma concentrations of apoM were semi-quantitatively determined by dot-blotting analysis, and total serum lipid levels were quantified using an automated RA-1000 (Technician, USA). The genotyping of rs805297 of apoM was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Genotype and allele frequencies were not significant (P?=?0.5798 and 0.3834, respectively) between cases and controls. Compared with the wild-type C/C genotype, carriers of the C/A and A/A genotypes did not have an increased risk of CAD, as determined by multiple logistic regression analysis, after adjustment for age, sex, BMI, history of smoking, hypertension and hypercholesterolemia. (CA, odds ratio?=?0.49, 95% confidence interval 0.15-1.87, P?=?0.462; AA, odds ratio?=?0.51, 95% confidence interval 0.13-1.68, P?=?0.534). The plasma concentration levels of apoM did not differ significantly among carriers of the three genotypes between two groups. Lastly, control subjects with A/A genotypes had lower total levels of HDL cholesterol than did those with C/C genotypes. CONCLUSIONS: The results presented here suggest that the rs805297 SNP is not associated with an increased risk of developing CAD, although it does independently correlate with dyslipidaemia in Han Chinese individuals.

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Decreased activities of apolipoprotein m promoter are associated with the susceptibility to coronary artery diseases.

Publications

Decreased activities of apolipoprotein m promoter are associated with the susceptibility to coronary artery diseases.

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