BACKGROUND: Several studies have focused on the association between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism; however, the results are conflicting. The effects of statins show significant variability between individuals. This meta-analysis aimed to investigate the effects of the SLCO1B1 c.521T>C polymorphism on the lipid-lowering effects of statins. METHODS: We systematically searched PubMed and Web of Science to screen relevant studies. Meta-analysis was performed to identify the association between SLCO1B1 c.521 polymorphisms and the lipid-lowering effects of statinson the basis of the standard mean difference (SMD) and 95% confidence intervals (CIs). Additionally, we checked for heterogeneity (I 2) among studies and evidence of publication bias. We obtained eight studies including 2,012 wild genotype (T/T) and 526 variant genotype (T/C and C/C) cases. RESULTS: No significant difference was observed in the lipid-lowering efficacy of statins between the wildand variant genotypes of SLCO1B1, with a pooled SMD of 0.03 (95% CI: -0.07-0.13). Furthermore, there was no significant effect in the meta-analyses of the variant heterozygote, homozygote, and Chinese populations. Subgroup meta-analysis indicated that the timerequired for the statin to take effectdid notsignificantly affect the association between lipid-lowering efficacy of statins and SLCO1B1 c.521T>C polymorphism. However, thewild genotype improved the lipid-lowering efficacy of simvastatin with a pooled SMD of -0.26 (95% CI: -0.47- -0.05). CONCLUSIONS: No significant association was detected between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism, with the exception of simvastatin.
Alleles ; Databases, Factual ; Genotype ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Hyperlipidemias/drug therapy/genetics ; Polymorphism, Single Nucleotide ; Solute Carrier Organic Anion Transporter Family Member 1b1/*genetics

Aged ; Female ; Fluorobenzenes ; therapeutic use ; Humans ; Hyperlipidemias ; blood ; drug therapy ; genetics ; Polymorphism, Genetic ; genetics ; Pyrimidines ; therapeutic use ; Rosuvastatin Calcium ; Sulfonamides ; therapeutic use

BACKGROUNDAgeing is associated with increased incidence of dyslipidemia. To investigate potential molecular mechanisms, the effects of age and fibrate administration on peroxisome proliferator-activated receptor alpha (PPARalpha) expression in livers of young and old rats were studied.

METHODSA total of 16 young (2-month-old) and 16 old rats (24-month-old) were randomly assigned to a control group and fenofibrate group (fenofibrate in a total therapeutic dosage of 0.5% in ratio to each treated rat weight in 14 days). RT-PCR was applied to evaluate hepatic mRNA expression of PPARalpha and its target genes. Western blotting was used to determine PPARalpha protein level in liver tissue.

RESULTSWhen compared with 2-month-old rats, the liver tissue from 24-month-old rats showed reduced expression of PPARalpha mRNA (52%, P < 0.05) and protein (109%, P < 0.01). Consequently, the mRNA levels of PPAR target genes, LPL, ACO, ACS and CPT-1 were markedly lowered by 19%, 8%, 13% and 9% respectively, and apoCIII increased by 24% in livers from 24-month-old rats, compared with values obtained from 2-month-old rats (P < 0.05). Fenofibrate therapy significantly lowered plasma triglyceride and total cholesterol levels in old rats, accompanied with improvement in hepatic expression of genes, including LPL, ACO, ACS, CPT-1 and apoCIII, but no change was found in PPARalpha expression in livers from either 24-month or 2-month-old rats.

CONCLUSIONSThe decrease in the hepatic PPARalpha expression is probably directly related to the lipid metabolic disturbances observed in old animals. The beneficial effects of fenofibrate administration in old rats suggests that fibrates may be useful for treating lipid disturbances in old people.

Aging ; metabolism ; Animals ; Fenofibrate ; pharmacology ; therapeutic use ; Hyperlipidemias ; drug therapy ; etiology ; Lipids ; blood ; Liver ; metabolism ; Male ; PPAR alpha ; genetics ; Rats ; Rats, Sprague-Dawley

Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide (WIP) was isolated and identified from the sclerotium of Poria cocos, a widely used Traditional Chinese Medicine. WIP was confirmed to be a (1-3)-β-D-glucan with an average Mw of 4.486 × 10 Da by NMR and SEC-RI-MALLS analyses. Furthermore, oral treatment with WIP from P. cocos significantly improved glucose and lipid metabolism and alleviated hepatic steatosis in ob/ob mice. 16S DNA sequencing analysis of cecum content from WIP-treated mice indicated the increase of butyrate-producing bacteria Lachnospiracea, Clostridium. It was also observed that WIP treatment elevated the level of butyrate in gut, improved the gut mucosal integrity and activated the intestinal PPAR-γ pathway. Fecal transplantation experiments definitely confirmed the causative role of gut microbiota in mediating the benefits of WIP. It is the first report that the water insoluble polysaccharide from the sclerotium of P. cocos modulates gut microbiota to improve hyperglycemia and hyperlipidemia. Thereby, WIP from P. cocos, as a prebiotic, has the potential for the prevention or cure of metabolic diseases and may elucidate new mechanism for the efficacies of this traditional herbal medicine on the regulation of lipid and glucose metabolism.
Animals ; Bacteria ; classification ; genetics ; isolation & purification ; metabolism ; Butyrates ; metabolism ; Fatty Liver ; drug therapy ; Fungal Polysaccharides ; chemistry ; pharmacology ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; genetics ; Hyperglycemia ; drug therapy ; Hyperlipidemias ; drug therapy ; Intestines ; drug effects ; microbiology ; Male ; Metabolic Syndrome ; drug therapy ; Mice ; Mice, Obese ; Prebiotics ; Wolfiporia ; chemistry

OBJECTIVETo explore the influence of apolipoprotein E (ApoE) gene polymorphism on the lipid metabolism regulatory effect of Xuezhikang Capsule (XZKC).

METHODSApoE polymorphism of 74 patients with hyperlipidemia was detected by gene sequencing method, and their plasma levels of total cholesterol (TC), triglyceride (TG), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C) were determined before and after they received a 6-week treatment of XZKC, for analyzing the relationship between ApoE gene polymorphism and the changes of various blood lipids associated indices.

RESULTSThe effect of XZKC on reducing TG in the epsilon2 allele (E2/E2 and E2/E3 genotypes) was higher than that in the E3/E3 genotypes and epsilon4 allele (E3/E4 and E4/E4 genotypes), while on increasing HDL-C, it showed more effect in the epsilon4 allele (E3/E4 and E4/E4 genotypes) than that in the epsilon2 allele (E2/E2 and E2/E3 genotypes) and E3/E3 genotypes.

CONCLUSIONPatients' ApoE gene polymorphism could influence the lipid regulatory effect of XZKC, embodying mainly by raising HDL-C and reducing TG in patients with different ApoE genotypes to different extents.

Adult ; Aged ; Apolipoproteins E ; genetics ; Cholesterol, HDL ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Genotype ; Humans ; Hyperlipidemias ; blood ; drug therapy ; genetics ; Lipid Metabolism ; drug effects ; Male ; Middle Aged ; Polymorphism, Genetic ; Triglycerides ; blood

To study the effects of alkaloids from Coptidis Rhizoma on low-density lipoprotein receptor (LDLR) mRNA expression and antihyperlipedemic levels. The LDLR mRNA expression were detected by real time fluorescence quantitative PCR, and the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-c) and high-density lipoprotein cholesterol (HDL-c) in serum were measured at the first and last examination. The results show that, after the drug treatment, compared with the model group, each drug group showed a lipid-lowering effect. Especially, coptisine, palmatine, jatrorrhinze were significantly reduced TC, TG, LDL-c (P < 0.05, P < 0.01), and increased HDL-c (P < 0.01). In addition, they also increased mRNA expression of the LDLR in liver and HepG2 cells. The results showed that alkaloids from Coptidis Rhizoma can regulate lipid metabolism disorder, and coptisine have the best lipid-lowering effect.
Alkaloids ; administration & dosage ; Animals ; Cholesterol ; metabolism ; Cricetinae ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hyperlipidemias ; drug therapy ; genetics ; metabolism ; Hypoglycemic Agents ; administration & dosage ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Lipoproteins, LDL ; metabolism ; Mesocricetus ; Receptors, Lipoprotein ; genetics ; metabolism ; Triglycerides ; metabolism

OBJECTIVETo investigate the effect of apolipoprotein B (apoB) and E (apoE) genetic variations on lipid profile at baseline (before treatment), and also on the subsequent response to simvastatin therapy.

METHODSEighty-eight patients with hyperlipidemia were treated with simvastatin 5mg daily. The plasma levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and apo B were measured pre-treatment and at the end of the 4th, 8th and 12th post-treatment week. Polymorphisms of apoB at XbaI locus and apoE were determined by restriction fragment length polymorphism (RFLP).

RESULTSIn all patients, relative frequencies of X- allele and X+ allele were 0.943 and 0.057 for apoB gene respectively. For apoE gene the relative frequency of epsilon2 allele was determined as 0.182, epsilon3 as 0.580 and epsilon4 as 0.238. The reduction in TC level was more prominent in patients carrying X- allele than in those with X+ allele following treatment (-23. 9% vs. -13. 6%, P < 0. 05). Compared with patients carrying epsilon3 or epsilon4 allele, those with epsilon2 allele showed a significantly higher percentage in reduction of apoB level after treatment (P < 0.05).

CONCLUSIONThe relative frequency of apoB X+ allele is high in patients with hyperlipidemia, in whom the TC-lowering efficacy is decreased following treatment of simvastatin. The relative frequencies of epsilon2 and epsilon4 are also high in hyperlipidemic patients, and the epsilon2 allele is associated with reduction in apoB level during lipid-relating therapy.

Aged ; Alleles ; Apolipoproteins B ; genetics ; Apolipoproteins E ; genetics ; Cholesterol ; blood ; Cholesterol, LDL ; blood ; Female ; Gene Frequency ; Humans ; Hyperlipidemias ; blood ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Polymorphism, Restriction Fragment Length ; Simvastatin ; pharmacology ; therapeutic use ; Triglycerides ; blood

Rhubarb is a traditional Chinese medicine (TCM), wildly used in treating the disease of hyperlipidemia. However, its components are complicated, so that it is still difficult to clear the specific roles of its various components in blood lipids regulation in. So we decide to systematically study the anti- hyperlipidemia mechanism of rhubarb. We integrated multiple databases, based on entity grammar systems model, constructed molecular interaction network between the chemical constituents of rhubarb and hyperlipidemia. The network includes 231 nodes and 638 edges. Thus we infer the interactions of active targets and disease targets to clarify the anti-hyperlipidemia mechanism. And find that rhubarb can promote excretion of cholesterol; inhibit clotting factors and improve blood circulation; inhibit the release of inflammatory cytokines and maintain fat metabolism balance; inhibit cholesterol and triglyceride synthesis; and other ways to achieve lipid-lowering effect. Thus this study provides reference for novel drug development and component compatibility, and also gives a new way for the systematically study of acting mechanism of traditional Chinese medicine.
Animals ; Databases, Factual ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Regulatory Networks ; drug effects ; Humans ; Hyperlipidemias ; drug therapy ; genetics ; metabolism ; Hypolipidemic Agents ; administration & dosage ; chemistry ; Lipid Metabolism ; Rheum ; chemistry ; Signal Transduction ; drug effects

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. As a metabolic regulator, FXR plays key roles in bile acid and cholesterol metabolism and lipid and glucose homeostasis. Therefore, FXR is a potential drug target for several metabolic syndromes, especially those related to lipidemia disorders. In the present study, we identified small molecule SIPI-7623, a derivative of an extract from Oriental wormwood (Artemisia capillaris), and found that it specifically upregulated the expression of cholesterol-7-alpha-hydroxylase (CYP7A1), downregulated the expression of sterol-regulatory element-binding protein 1c (SREBP-1c) in the liver, and inhibited the expression of ileal bile acid binding-protein (IBABP) in the ileum of rats. We found that inhibition of FXR by SIPI-7623 decreased the level of cholesterol and triglyceride. SIPI-7623 reduced the levels of cholesterol and triglyceride in in vitro HepG2 cell models, ameliorated diet-induced atherosclerosis, and decreased the serum lipid content on rats and rabbits model of atherosclerosis in vivo. Furthermore, SIPI-7623 decreased the extent of atherosclerotic lesions. Our resutls demonstrated that antagonism of the FXR pathway can be employed as a therapeutic strategy to treat metabolic diseases such as hyperlipidemia and atherosclerosis. In conclusion, SIPI-7623 could be a promising lead compound for development of drugs to treat hyperlipidemia and atherosclerosis.
Animals ; Artemisia ; chemistry ; Atherosclerosis ; drug therapy ; genetics ; metabolism ; Cholesterol ; metabolism ; Cholesterol 7-alpha-Hydroxylase ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hyperlipidemias ; drug therapy ; genetics ; metabolism ; Hypolipidemic Agents ; administration & dosage ; Liver ; drug effects ; metabolism ; Male ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; antagonists & inhibitors ; genetics ; metabolism ; Sterol Regulatory Element Binding Protein 1 ; genetics ; metabolism ; Triglycerides ; metabolism

OBJECTIVETo explore the effect of polymorphism in codon Ala54Thr of human intestinal fatty acid-binding protein gene (IFABP) on the therapeutic efficacy of fenofibrate.

METHODSTotally 147 patients with hyperlipidemia [72 men mean age: (56.2 +/- 8.63) years; 75 women mean age: (58.4 +/- 9.12) years] were enrolled. IFABP genotypes were detected by polymerase chain reaction, Hha I digestion, and sequencing. Four weeks before and after treatment, the levels of fasting serum total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), apolipoprotein A I (apoA I) and apolipoprotein B (apoB) were detected with biochemical techniques.

RESULTSThe frequency of IFABP genotype was 0.47 for A/A, 0.37 for A/T, and 0.16 for T/T, and the allelic frequency was 0.65 for A and 0.35 for T. No significant different was found in lipid levels in every genotype before treatment (P > 0.05). After 4 weeks of treatment, the levels of TC, TG, LDL-C, and apoB significantly decreased (P < 00.01), and the levels of HDH-C and apoA I significantly increased (P < 0.01). The total therapeutic efficacy on A54A and A54T were 97% and 95%, respectively. In the patients with T54T genotype after treatment, no significant difference in lipids levels was found except TG (P < 0.05), and the total efficacy was only 38%. The total therapeutic efficacies of fenofibrate on A54A and A54T were higher than those of T54T, and there was significant different between A54A and T54T (P < 0.01).

CONCLUSIONThe polymorphism of human IFABP gene in hyperlipidemia is related with the therapeutic efficacy of fenofibrate, and the T54T IFABP genotype may have strong negative effect on such efficacy.

Aged ; Apolipoproteins ; blood ; Fatty Acid-Binding Proteins ; genetics ; Female ; Fenofibrate ; therapeutic use ; Gene Frequency ; Genotype ; Humans ; Hyperlipidemias ; blood ; drug therapy ; genetics ; Hypolipidemic Agents ; therapeutic use ; Lipids ; blood ; Male ; Middle Aged ; Polymorphism, Genetic ; Treatment Outcome