Association between a new SNP in proximal promoter region of apolipoprotein M and susceptibility of coronary artery diseases in Han Chinese population / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between genetic polymorphisms of proximal promoter region of apolipoprotein M (apoM) gene and susceptibility of coronary artery diseases (CAD) in Han Chinese population.</p><p><b>METHODS</b>Two pairs of primers were designed according to the sequence (GenBank accession nos. EU030444.1) and the PCR products of apoM proximal promoter region were directly sequenced. Two hundred and six patients [165 males, mean age (61.9 ± 9.2) years old] diagnosed with CAD according to the results of angiography (a lesion was classed as being significant when stenosis was more than 50%) were enrolled in the present study, 209 age- and gender-matched patients[157 males, mean age (60.4 ± 9.1) years old] without CAD according to the results of angiography were selected as the control group. The allelic frequencies and genotype distributions of polymorphism in CAD and non-CAD patients were analyzed. Furthermore the wide-type and mutant promoter region of apoM were cloned into the luciferase expression vector pGL3, respectively. Luciferase reporter assay was used to detect the activity of apoM promoter.</p><p><b>RESULTS</b>A new deletion mutation -724delC in apoM promoter was found. The frequency of Del C allele was 8.0% in CAD patients and only 4.1% in the non-CAD controls (OR = 2.054, 95%CI 1.125-3.749, P = 0.017). The mean TC level was lower in groups with wide-type homozygotes compared to the mutant allele carriers [ (6.04 ± 0.90) mmol/L vs. (4.95 ± 1.00)mmol/L, P < 0.01]. -724delC mutant showed obvious decreased luciferase activities (1.13 ± 0.25 vs. 2.11 ± 0.15, P = 0.009).</p><p><b>CONCLUSION</b>It is reasonable to speculate that -724delC could affect the activity of the apoM promoter and downregulate apoM expressions, therefore, influence the susceptibility of CAD in this patient cohort.</p>

Estrogen increases apolipoprotein M through estrogen receptor / 中华内分泌代谢杂志

Objective To explore the effects of estrogen on apolipoprotein M ( apoM ).Methods ApoM mRNA was assayed in HepG2 cells by RT-PCR after incubation of estrogen with or without estrogen receptor antagonist at different concentrations and durations.SD female rats were divided into five groups:OVX group,Sham group,OVX+ EB group,normal group and normal + EB group.From a week of being operated,the rats were injected subcutaneously estradiol beuzoate or vehicle.After 12-hrs fasting,serum levels of triglycerides (TG),LDL-cholesterol,HDL-cholesterol,total cholesterol ( TC ) at months 1,2 and 3 after operation were measured.The expression of apoM in rats was detected by using real time RT-PCR and Western blot.Results Estrogen increased mRNA levels of apoM and apoAI in the HepG2 cells with a dose- and time-dependent manner,which could be abolished by addition of estrogen receptor antagonist.Serum apoM,TG,TC,HDL and LDL levels were significantly increased in the ovariectomized or normal rats which received estrogen treatment than those in OVX or normal group rats at month 1 after treatments.Conclusions Estrogen upregulates apoM expression via its receptor.