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.

Meta-Analysis on the Correlation Between APOM rs805296 Polymorphism and Risk of Coronary Artery Disease

“…Subsequently, after the adjustment of susceptibility factors for CAD, the C allele was found to be an independent risk factor for the occurrence of ACS [ 25 ]. In addition, some other studies also obtained results similar to those mentioned above [ 18 , 22 , 23 , 26 ]. In contrast, Zheng et al found no statistically significant difference in distribution of 3 genotypes of ApoM rs805296 polymorphism, including TT, TC, and CC, between case and control groups, and concluded that rs805296 might not be correlated with the development of CAD [ 24 ].…”

“…Initially, 81 records were identified through the computer search, and 36 remained after excluding 8 studies not on humans and 37 apparently irrelevant ones. Through the subsequent exclusion for reviews and letters (7), without full texts (3), duplicates (5), not about ApoM rs805296 polymorphism (8) and without original data (6), we eventually included 7 studies in the quantitative synthesis [ 18 , 21 – 26 ]. The primary features of eligible studies are presented in Table 1 .…”

C deletion of the SLC39A8 gene polymorphism (rs74650330) increases the risk of coronary artery disease in individuals with low LDL cholesterol levels

“…However, the present study had a number of limitations. Certain patients may receive lipid-lowering therapy prior to diagnosis with CAD, suggesting why the TC levels were lower in patients with CAD than in the control group subjects in the current study, which differed from previously published results [28]. We had a limited sample size to detect SNPs, and weak effects can be observed when considering multiple corrections.…”

Hyperglycemia-induced downregulation of apolipoprotein M expression is not via the hexosamine pathway

“…The serum apoM concentration is significantly reduced in diabetic patients [ 6 ]. Single nucleotide polymorphism (SNP) T-778C, C-724del and T-855C in the proximal promoter region of apoM gene have significant associations with CAD and type-2 diabetes among Han Chinese [ 7 , 8 ]. Moreover, apoM is reduced in diabetic rats and exogenous insulin administrations could partially reverse the abnormal apoM expression [ 9 ].…”