Warfarin is one of the most frequently prescribed oral anticoagulant. Many researches have shown that the genotypes have been strongly associated with warfarin maintenance doses. Especially, it has been accepted in academia that cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 subunit (VKORC1) could affect the warfarin maintenance doses. There are also many other genotypes that were reported to be related to warfarin doses, but the results have been in controversial so far. The studies found that the dose formula which contained the genetic factors and clinical information could accurately predict the maintenance dose of warfarin, however, its usefulness is suspected due to the inconsistent results of clinical trials. Large-sample and multi-center studies are necessary to verify the specific effects of gene and non-gene factors to warfarin dose; at the same time, testing constructed models or building new models help to improve the explained percentages of individual differences.
ObjectiveTo study the correlation between CYP1A1 MspI gene polymorphisms and the risk of breast cancer (BC) in Chinese population.MethodsThe case-control studies on the correlation between polymorphisms of CYP1A1 MspI and BC in Chinese population were electronically retrieved in online English database (PubMed and Web of Science) and Chinese database (Chinese National Knowledge Infrastructure, Wanfang, and VIP database) from the date of their establishment to December 31, 2018. Two reviewers completed literature screening according to the inclusion and exclusion criteria, data extraction, and methodological quality assessment of the included studies independently. Reman 5.3 software was used to meta-analysis.ResultsA total 14 case-control studies involving 3 372 cases and 3 510 controls were finally included. The meta-analysis results showed that the CYP1A1 MspI gene polymorphism was associated with BC in Chinese population. Dominant genetic model [OR=1.24, 95%CI was (0.98, 1.58), P=0.08] and heterozygote model [OR=1.11, 95%CI was (0.89, 1.39), P=0.37] had no association with BC in Chinese population, while recessive genetic model [OR=1.66, 95%CI was (1.28, 2.14), P=0.000 1], homozygote model [OR=1.76, 95%CI was (1.26, 2.45), P=0.000 9], and allele contrast genetic model [OR=1.30, 95%CI was (1.08, 1.56), P=0.005] increased the risk of BC in Chinese population.ConclusionIt is demonstrated that in Chinese population, CYP1A1 MspI gene polymorphisms related to the risk of BC, recessive genetic model, homozygote model, and allele contrast genetic model might be the risk factor for BC.
ObjectiveTo investigate the relationship between the CYP3A5 genotyping and the drug metabolism of tacrolimus after operation in adult liver transplantation.MethodsNinety-eight adult patients with liver transplantation in Tianjin First Center Hospital were selected as subjects. The blood samples of liver transplantation recipients and donor were collected before operation, and then tested the CYP3A5 genotyping by PCR method. The weekly body mass, tacrolimus dose, and drug valley concentration of the patients were monitored in 1, 2, 3, and 4 weeks after operation, to calculate the tacrolimus concentration/dose ratio. And then compared the effects of different genotyping of donor and receptors on tacrolimus concentration/dose ratio.ResultsIn the CYP3A5 genotyping of 98 patients with liver transplantation and the corresponding donors, GG type was the most and AA type was the least, the distribution of alleles was in accordance with the genetic law, and the difference was not statistically significant (P>0.05). According to the donor genotype, the results showed that there was a significant correlation between tacrolimus concentration/dose ratio and donor or recipients CYP3A5 genotype at 1, 2, 3, and 4 weeks after liver transplantation, and there was significant difference among the three groups (P<0.05): GG>AG>AA. According to the combined grouping of donor and receptor genotype, the results showed that there was significant difference in tacrolimus concentration/dose ratio among A*/A*, A*/GG, GG/A*, and GG/GG group (P<0.05), while there was significant difference in tacrolimus concentration/dose ratio between GG/GG and A*/A* group (P<0.01), the tacrolimus concentration/dose ratio was highest in GG/GG group and lowest in A*/A* group.ConclusionsThe CYP3A5 genotyping of the recipient and donor can affect the blood concentration of tacrolimus after liver transplantation, and the CYP3A5 GG genotype is more likely to reach the target plasma concentration than the other genotypes, that the detection of donor and recipient CYP3A5 genotype in patients with liver transplantation can provide a reference for individualized treatment of tacrolimus after liver transplantation.