Correlation analysis between ApoM gene promoter polymorphisms and coronary heart disease
Summary Objectives: 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 b 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 electophoretic 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 mg/ 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 typecould bind to the AP 2a. Interference and overexpression of AP 2 increased and decreased luciferase activities of the wild and mutant types to different degrees. Conclusion: ApoM may be a biomarker of CAD. ApoM 855 T C substitution provides binding sites for AP 2a and reduces ApoM transcription activity.
Cardiovascular journal of Africa