Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response

Abstract

ABSTRACT. Oral anticoagulants of the coumarin type have an inconveniently narrow therapeutic window, making their use difficult. In Mexico, genetic variables that participate in the heterogeneity of the therapeutic response remain poorly investigated. With the focus on warfarin, extensive pharmacogenomic studies have been performed, including those on the CYP450 family and APOE. The objective of this study was to determine the contribution of CYP2C9, CYP2C19, and APOE polymorphisms to the variations in response to the doses of acenocoumarol, which is the main anticoagulant prescribed to the Mexican population. The polymerase chain reaction-restriction fragment length polymorphism method was applied to identify *2 and *3 of CYP2C9, *2 of CYP2C19, and APOE variants. The genetic distribution of every polymorphism tested showed high variability when compared with other populations worldwide. Our results showed statistical differences only in the CYP2C19 gene between the *1*1 and *1*2 groups, with effective acenocoumarol doses of 2.56 ± 1.34 mg/day vs 1.35 ± 0.84 mg/day (P = 0.005), respectively. Multiple regression analysis, including patient age and both the CYP2C9 and CYP2C19 genes, showed that these variables explained more than 20% of the dose variations. This is the first report in Mexico searching for the relationship between CYP450 and APOE polymorphisms and the dose requirements of acenocoumarol. Our results suggest that, in the Mexican population, CYP2C19 is more involved in acenocoumarol metabolism than CYP2C9 and APOE. Besides considering the age factor, pharmacogenetic testing for CYP2C19*2 before initiating acenocoumarol treatment could lead to a safer anticoagulation therapy in Mexican patients.

CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy

“…[29][30][31][32] In both our patient and volunteer MM samples, we observed a predominance of the wild-type CYP2C19*1 allele, a low frequency of CYP2C19*2 and an absence of CYP2C19*3 allele, as it has been previously reported. [33][34][35][36][37][38] The frequency of CYP2C19*17 allele found in the present study (MM from Central Mexico) shows a minor nonsignificant difference from that found in a recent report in MM from the state of Jalisco (0.09 and 0.14, respectively). 38 The frequency of ABCB1 3435C4T in the MM population studied here is similar to that found in previous reports.…”

Influence of CYP2C19 on Helicobacter pylori eradication in Brazilian patients with functional dyspepsia

“…A recent study conducted in Southern Brazil (at the same geographic location sampled in this study) reported HomEM, HetEM, and PM genotype frequencies of 71.5, 26.3, and 2.2%, respectively (Kohlrausch et al, 2014). Other studies conducted in western populations have also reported similar CYP2C19 genotype distributions (Ishizaki and Horai, 1999;Kurose et al, 2012;Nastasi-Catanese et al, 2013). However, a significantly different distribution was reported in Asian populations, where the frequency of the PM genotype was ~23% higher than that in western populations (approximately 5%) (Ishizaki and Horai, 1999;Hirota et al, 2013).…”

Research Article Infertility caused by an association between <em>Arg72Pro</em> polymorphism of the <em>p53</em> gene and <em>Glu298Asp</em> of the <em>eNOS</em> gene in patients with endometriosis

“…The risks of this disease in women who have affected relatives are greater compared to the general population. Multiple genes have been associated with endometriosis and among them are the cytochrome P450 (CYP) family, tumor suppressor genes, estrogen regulatory genes, proinflammatory cytokines, vascular function regulators and pro-angiogenic genes (Nastasi-Catanese et al, 2013).…”