藥物對變異型脂蛋白元A5 c.553G>T之影響

Abstract

Hypertriglyceridemia (HTG) is an independent risk factor for the development of cardiovascular disease and is often associated with diabetes, inflammation and the metabolic syndrome. Recently, apolipoprotein A5 (APOA5) was identified as a novel member of the APOAI/CIII/AIV gene cluster. Data from mice over-expressing or lacking apoAV provide direct evidence that this apolipoprotein plays a crucial role in triglyceride metabolism. Moreover, plasma triglyceride levels were found to be strongly associated with APOA5 polymorphisms. We previously identified genetic variant in Chinese people, c.553G > T in the APOA5 gene which causes a substitution of a cysteine for a glycine residue at amino acid residue 185 is associated with increased TG levels, also a risk factor for coronary artery disease. The human APOA5 gene is regulated by transcription factors known to affect triglyceride metabolism such as PPARα, RORα, LXR ,SREBP-1c and thyroid receptorβ and this supports its function. To date, the triglyceride lowering action of apoA5 is attributed to the activation of lipoprotein lipase (LPL) and an acceleration of very low density lipoprotein catabolism. Recent findings indicate that APOA5 could also influence cholesterol homeostasis and probably play a role in hypertriglyceridemia associated with diabetes and inflammation. Considering clinical application, we want to examine whether APO A5 is the new drug target for HTG. For that, we examined drugs and chemicals effects on APOA A5 promoter activity. Further, whether these new strategies for curing HTG are practicable therapies. All drugs and chemicals increased the expression of APOA5 promoter from 118.4 % to 453.9 % . While drugs or chemicals increased the wild type and variant apoAV concentractions from 62.5 % to 208.9 % and 39 % to 273.1 % respectively, the LPL-activating abilities of drugs-treated apoAV remained the same among wild type, variant and control. Maybe proper methodology of LPL activity assay is needed for further studies. Further studie is needed to explore the mechanism.