Azaserine synthesis Pharmacogenomics is the study of the rol
Pharmacogenomics is the study of the role of the Azaserine synthesis in drug response. It was reported that the effectiveness of atorvastatin was affected by genetic factors.26, 27 In previous studies, there are many genetic polymorphisms related to the efficacy of atorvastatin. Cerda et al reported that SCARB1 polymorphism was associated with changes in blood lipid levels in Brazil, and c.1050C> T SNP was associated with atorvastatin lipid-lowering reactions. Yue et al reported that there was a relationship between APOA5, LPL, and CETP gene polymorphisms and the therapeutic effect of atorvastatin in patients with IS in China. Fukunaga et al found that genetic polymorphisms affected not only the efficacy of atorvastatin but also with adverse reactions. In addition to the aforementioned genes, the cholesterol-lowering effect of atorvastatin was also influenced by polymorphisms in the CYP450 family of genes.
CYP450 is a group of structurally and functionally related superfamily genes. It plays an important role in the metabolism of endogenous (eg, fatty acids, steroids, prostaglandins, bile acids) and exogenous (eg, drugs, environmental carcinogens, food additives) substances. There are great achievements in the field of drug genomics in CYP450, and all the CYP450 major family members associated with drug metabolism have been identified. At the same time, it has been recognized that the widespread polymorphism of CYP450 is the main cause of individual differences in drug response.
CYP2D6 is located on human chromosome 22, which contains 9 exons and 1 reading frame. It is highly polymorphic in the human population. CYP2D6 is very important for the metabolism of clinically used drugs. There are ~20% to 25% of drugs metabolized by the enzyme. It was shown that the CYP2D6 gene polymorphism was associated with the muscle toxicity of atorvastatin. It has also been reported that LDL-C levels were significantly decreased with the GG genotype compared with the AG and AA genotypes after treatment with simvastatin for 8 weeks. In addition, CYP2D6 polymorphisms reportedly have a different influence on the cholesterol-lowering effect of simvastatin in various studies.33, 34
At present, there have been no studies on the relationship between CYP2D6 gene polymorphism and the lipid-lowering effect of atorvastatin. Our results showed that the rs1065852 in CYP2D6 influences the effectiveness of atorvastatin, and the GG genotype had a better response to atorvastatin therapy, which was consistent with the effect of simvastatin therapy. All these data suggest that the patients with IS carrying the GG genotype may consider taking less atorvastatin to avoid the side effects of this drug. CYP3A4 is an important part of the CYP450 superfamily. CYP3A4 is involved in the metabolism of most statins and often investigated in statin pharmacogenetics. It has been found that the polymorphism of CYP3A4 is associated with lipid-lowering efficacy of atorvastatin. Our study showed that rs2242480 (CYP3A4) showed a moderate affected ΔLDL under the dominant model without Bonferroni correction. It suggested that the rs2242480 in CYP3A4 might affect the lipid-lowering efficacy of atorvastatin. In addition, the combined effects of rs1065852 and rs2242480 on the lipid-lowering efficacy of atorvastatin in our study further confirmed that CYP3A4 had a connection with the metabolism of atorvastatin, even though further replicate studies are needed, with confirmation in a larger population.
Conclusions Our study suggests that CYP2D6 affects treatment with atorvastatin in patients with IS. In addition, there might be a trend that the rs2242480 in CYP3A4 may affect the lipid-lowering efficacy of atorvastatin. However, a large number of well-designed studies are needed to validate the association.
Conflicts of Interest
Introduction Among different reported species of Swertia in India, Swertia chirata (Folk name: Chirata) Buch-Ham (Gentianaceae) is considered as the most important medicinal plant and are still being used a bitter tonic, stomachic, febrifuge and anthelmintic, anti-periodic, cathartic, asthma, leucorrhoea, analeptic, stomachic, mitigate inflammation, relaxing to pregnant uterus and never ending fevers in ISM and Traditional Chinese Medicine (TCM) (Joshi and Dhawan, 2005, Kirtikar and Basu, 1984). S. chirata contains a large number of therapeutically active phytoconstituents such as xanthones, flavonoids, terpenoids, iridoids, secoiridoid, glycosides, swertiamarin and ursolic acid (Phoboo et al., 2010, Joshi and Dhawan, 2005). Ursolic acid possesses anti-diabetic property which is reported by Wu et al. (2010). It has been reported that SC possess hypoglycaemic (Suryawanshi et al., 2006), anti-inflammatory (Banerjee et al., 2009), hepatoprotective (Nagalekshmi et al., 2011), anticancer (Saha et al., 2004), antibacterial (Kumar et al., 2010), antioxidant (Chen et al., 2011), antileishmanial (Ray et al., 1996) and antimalarial activity (Bhat and Surolia, 2001). Multidrug combination therapy is very common and people consume conventional medicines along with herbals without consulting with physician (Subehan et al., 2011). According to World Health Organization (WHO), Traditional medicines (TM) are still being used by 75–80% of world population and up to 7000 chemical compounds used in phytotherapy were derived from medicinal plants (Sieniawska et al., 2013).