ABSTRACT
The human adenosine triphosphate-binding cassette transporter A1(ABCA1)gene is highly polymorphic.Some polymorphisms in promoters (rs2422493 ,rs2740483 ,etc. ) and exons (rs2230806 ,rs4149313 ,etc. )have been reported to be significantly associated with coronary heart disease(CHD ). In terms of the underlying mechanisms ,ABCA1 gene polymorphisms might be associated with CHD through modulating the levels of high-density lipoprotein cholesterol and other lipids ,or through changing ABCA1 protein structure and function. In this article ,the association of ABCA1 gene polymorphisms with CHD and the underlying mechanisms are reviewed.
ABSTRACT
[Objective]To explore the possible effects of the apolipoprotein A5(APOA5)gene rs2075291 and rs3135507 poly-morphisms on plasma lipid levels and the severity of coronary stenosis in patients with coronary heart disease(CHD)in Chinese Han people.[Methods]Polymerase chain reaction-restriction fragment length polymorphism method(PCR-RFLP)was used to identify the genotypes of the rs2075291 or rs3135507 polymorphism for the 324 patients with CHD and the 152 CHD-free controls,and the lipid levels between the genotypes were compared. The severity of coronary stenosis was assessed by the Gensini scoring system ,and the associations of the rs2075291 and rs3135507 polymorphisms as well as other factors with the Gensini scores were analyzed by mul-tivariate linear regression.[Results]The CHD patients had higher prevalence of hypertension ,and higher levels of triglycerides (TG),total cholesterol(TC),apolipoprotein B100(APOB100),lipoprotein(a)[Lp(a)],TG/high-density lipoprotein cholesterol (HDL-C),TC/HDL-C,low-density lipoprotein cholesterol(LDL-C)/HDL-C and APOB100/apolipoprotein AI(APOAI),and low-er levels of HDL-C and APOAI than the controls(P 0.05).[Conclusion]The APOA5 rs2075291 polymorphism had significant effects on plasma lipid levels,but no effects on the occurrence and development of CHD. Further multicenter case-control studies with large samples are needed to validate these findings.
ABSTRACT
Objective: To investigate the effect of the gene interfering technology on fatty acid synthase (FAS) gene silencing for lipid contents in human hepatic cell line HepG2 and to study the lipid metabolism related gene expression in HepG2 cells. Methods: A total of 3 pairs of small interfering RNA (siRNA) targeting different sequences of FAS mRNA were synthesized as FAS-siRNA-1, FAS-siRNA-2 and FAS-siRNA-3, meanwhile, 2 controls were established as Blank control group, in which HepG2 cells were not treated, and Negative control group, in which HepG2 cells were transfected by non-effective siRNA. The mRNA, and protein expression levels of FAS in HepG2 cells were examined by real-time lfuorescence quantitative RCR and Western blot analysis to screen the most effective pair of siRNA for FAS gene silencing; and that speciifc siRNA was transtected to HepG2 cells for 48 hours to detect the intra-/extra-cellular TG, TC levels and the mRNA expression related to lipid metabolism in HepG2 cells. Results: The screening experiment indicated that FAS-siRNA-3 was most effective for FAS gene silencing. Compared with Blank control group, the mRNA and protein expressions in FAS-siRNA-3 transfected HepG2 cells (Transfected group)decreased to (52.33 ± 3.07) % and (51.57 ± 3.14) % respectively. Compared with Blank control group, Transfected group had the reduced intra-/extra-cellular TG levels and reduced extracellular TC level; while increased mRNA expression of hepatic lipase,P<0.0001 and decreased mRNA expression of TG transfer protein in HepG2 microsome,P<0.05. Conclusion: FAS gene silencing could signiifcantly decrease the intra-/extra- cellular TG level and extracellular TC level in HepG2 cells, those ifndings need to be conifrmed by furtherin vivo andin vitro studies.