AIM: The aim of this meta-analysis was to evaluate the effect of statin therapy on plasma FFA concentrations in a systematic review and meta-analysis of controlled clinical trials. METHODS: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched (from inception to February 16 2015) to identify controlled trials evaluating the impact of statins on plasma FFA concentrations. A systematic assessment of bias in the included studies was performed using the Cochrane criteria. A random effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Random effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of potential moderators. RESULTS: Meta-analysis of data from 14 treatment arms indicated a significant reduction in plasma FFA concentrations following treatment with statins (weighted mean difference (WMD) -19.42%, 95% CI -23.19, --15.64, P < 0.001). Subgroup analysis confirmed the significance of the effect with both atorvastatin (WMD -20.56%, 95% CI -24.51, -16.61, P < 0.01) and simvastatin (WMD -18.05%, 95% CI -28.12, -7.99, P < 0.001). Changes in plasma FFA concentrations were independent of treatment duration (slope -0.10, 95% CI -0.30, 0.11, P = 0.354) and magnitude of reduction in plasma low density lipoprotein cholesterol concentrations (slope 0.55, 95% CI -0.17, 1.27, P = 0.133) by statins. CONCLUSIONS: The results of the present study suggest that statin therapy may lower plasma FFA concentrations. The cardiovascular and metabolic significance of this finding requires further investigation.
- MeSH
- kardiovaskulární nemoci farmakoterapie metabolismus MeSH
- kyseliny mastné neesterifikované krev metabolismus MeSH
- LDL-cholesterol krev MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- statiny farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
PURPOSE: Colorectal cancer is routinely treated with a 5-fluorouracil (5-FU)-based chemotherapy. 5-FU incorporates into DNA, and the base excision repair (BER) pathway specifically recognizes such damage. We investigated the association of single-nucleotide polymorphisms (SNP) in the 3'-untranslated regions (UTR) of BER genes, and potentially affecting the microRNA (miRNA) binding, on the risk of colorectal cancer, its progression, and prognosis. SNPs in miRNA-binding sites may modulate the posttranscriptional regulation of gene expression operated by miRNAs and explain interindividual variability in BER capacity and response to 5-FU. EXPERIMENTAL DESIGN: We tested 12 SNPs in the 3'-UTRs of five BER genes for colorectal cancer susceptibility in a case-control study (1,098 cases and 1,459 healthy controls). Subsequently, we analyzed the role of these SNPs on clinical outcomes of patients (866 in the Training set and 232 in the Replication set). RESULTS: SNPs in the SMUG1 and NEIL2 genes were associated with overall survival. In particular, SMUG1 rs2233921 TT carriers showed increased survival compared with those with GT/GG genotypes [HR, 0.54; 95% confidence interval (CI), 0.36-0.81; P = 0.003] in the Training set and after pooling results from the Replication set. The association was more significant following stratification for 5-FU-based chemotherapy (P = 5.6 × 10(-5)). A reduced expression of the reporter gene for the T allele of rs2233921 was observed when compared with the common G allele by in vitro assay. None of the genotyped BER polymorphisms were associated with colorectal cancer risk. CONCLUSIONS: We provide the first evidence that variations in miRNA-binding sites in BER genes 3'-UTR may modulate colorectal cancer prognosis and therapy response.
- MeSH
- 3' nepřekládaná oblast * MeSH
- dospělí MeSH
- genetická variace * MeSH
- jednonukleotidový polymorfismus MeSH
- kolorektální nádory farmakoterapie genetika mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- oprava DNA genetika MeSH
- prognóza MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- vazebná místa MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
