RESUMO
A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I(2) = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
Assuntos
Cumarínicos/administração & dosagem , Sistema Enzimático do Citocromo P-450/genética , Polimorfismo Genético/genética , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Alelos , Hidrocarboneto de Aril Hidroxilases/genética , Estudos de Coortes , Cumarínicos/uso terapêutico , Estudos Transversais , Citocromo P-450 CYP2C9 , Família 4 do Citocromo P450 , Etnicidade , Humanos , Coeficiente Internacional Normatizado , Pessoa de Meia-Idade , Oxigenases de Função Mista/genética , Viés de Publicação , Fatores Sexuais , Vitamina K Epóxido RedutasesAssuntos
Fator VIII/antagonistas & inibidores , Hemofilia A/genética , Sistema Imunitário/metabolismo , Polimorfismo Genético , Alelos , Brasil , Antígeno CTLA-4/genética , Antígenos HLA-G/genética , Hemofilia A/imunologia , Humanos , Interleucina-10/genética , Interleucina-4/genética , Razão de Chances , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Receptores de Interleucina-4/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/genéticaRESUMO
The purpose of this study was to evaluate the thrombophilic genes in pregnant women with and without preeclampsia independently or in combination. In a prospective case-control study, we investigated four polymorphisms in thrombophilic genes in 75 women with mild or severe preeclampsia and 145 women with normal pregnancy. The genotype frequencies were assessed and the odds ratio (OR) calculated. When we analyzed the polymorphisms independently and the development of preeclampsia, no association was observed [methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, OR 2.07, 95% confidence interval (CI) 0.99-4.30; prothrombin mutation (F II) (GA or AA genotypes) OR 8.11, 95% CI 0.89-73.92; factor V Leiden (FV Leiden) OR 3.94, 95% CI 0.35-44.23; plasminogen activator inhibitor (PAI-1) 4G/4G genotype, OR 1.63, 95% CI 0.87-3.05] not even with severe preeclampsia subgroup analysis. However, when we investigated a possible interaction among these polymorphisms on the development of the preeclampsia, the OR for having one risk genotype, one or two genotype risk factors and two genotype risk factors compared to those without genotype risk factors were 1.97 (95% CI 1.08-3.59), 2.21 (95% CI 1.25-3.92) and 4.27 (95% CI 1.3-13.9), respectively. In conclusion, in the population analyzed, the presence of the genotype risk factors alone does not seem to be associated with the development of preeclampsia even in the severe presentation form. However, an interaction among the MTHFR, F II, FV and PAI-1 gene polymorphisms on the development of the preeclampsia was indicated.
