Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: A cross-ethnic comparative study

Luo, Huai Rong; Poland, Russell E.; Lin, Keh Ming; Wan, Yu‐Jui Yvonne

doi:10.1016/j.clpt.2006.03.003

Cited by 102 publications

(75 citation statements)

References 25 publications

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“…The CYP2C19*2 allele had a frequency of 7.9%, similar (P > 0.08) to Mexican-American, West Asian, and Southern and Eastern European populations (Luo et al, 2006;Kurose et al, 2012). The CYP2C19*2 allele frequency was statistically different from Western and Northern European; Southern, South-Eastern, and Southern Asian; Caucasian; and African populations (P ≤ 0.042), whose frequencies range from 14 to 29.8% (Kurose et al, 2012).…”

Section: Resultsmentioning

confidence: 90%

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

et al. 2013

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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.

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Section: Resultsmentioning

confidence: 90%

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

et al. 2013

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“…Calculated allele frequencies did not differ much from those reported earlier by other studies for Caucasians, as shown in Table 2. 17,18 Incidence of GVHD No statistic differences were found in the incidence of acute GVHD grade 2-4 for EMs, IMs and PMs with 28.2, 32.8 and 25%, respectively. The genotype of donors also had no significant influence on the incidence of GVHD grade 2-4 in patients.…”

Section: Frequency Of Ems Ims and Pmsmentioning

confidence: 94%

Cytochrome P450 2C19 loss-of-function polymorphism is associated with an increased treatment-related mortality in patients undergoing allogeneic transplantation

Elmaagacli

Koldehoff

Steckel

et al. 2007

Bone Marrow Transplant

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The polymorphic gene expression of CYP2C19 causes individual variability in drug metabolism and thereby in pharmacologic and toxicologic responses. We genotyped 286 patients and their donors for the CYP2C19 gene who underwent allogeneic transplantation for various diseases and analyzed their outcome. Patients were classified as: poor metabolizers (PMs; 3.1%), intermediate metabolizers (IMs; 24.5%) and extensive metabolizers (EMs; 72.5%). Patients genotyped as PMs had significant higher hepato-and nephrotoxicities compared to IMs or EMs. Maximum bilirubin and serum creatinine levels measured after transplant were approximately twofold higher than those of EMs or IMs. The increased toxicity resulted in an increased 4-year estimate for transplant-related mortality (TRM) with 50718.6% for PMs compared to 25.173.7% for EMs (Po0.018) and 22.7 75.6% for IMs (Po0.042), whereas no significant influence for relapse rate, overall survival or incidence of acute graftversus-host disease grade 2-4 were found between the groups. Multivariate analysis including all potential factors that might influence TRM confirmed that the genotype of CYP2C19 is an independent factor, which influenced TRM significantly. These results suggest that genotyping for CYP450 2C19 can help to identify patients with higher risk for TRM.

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“…5 Asians possess higher frequencies of *2 (28.9-31.2%) than Caucasians (12.7%) and African Americans (18.2%). 6 The second most important PM allele is CYP2C19*3, which carries a G-A nucleotide substitution in exon 4, creating a premature stop codon. 7 The prevalence rate of *3 in Asians ranges from 5.7 to 9.6%, whereas in Caucasians it is only 0.9%.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphism, linkage disequilibrium, haplotype structure and novel allele analysis of CYP2C19 and CYP2D6 in Han Chinese

Zhou

Lin

et al. 2009

Pharmacogenomics J

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The cytochrome P450 2C19 and 2D6 enzymes are predominantly found in the human liver, and have important functions in the metabolism of many different classes of commonly used drugs. Their genetic polymorphisms give rise to both important interethnic variability in metabolism and the risk of treatment failure or dose-dependent drug toxicity. To investigate genetic polymorphisms in CYP2C19 and CYP2D6 genes in Han Chinese, we sequenced regions of the 5 0 flanking region, exon, intron and 3 0 UTR from these two genes using 100 unrelated healthy Chinese Hans. We detected 48 genetic variants in CYP2C19. A total of 15 of them are novel, including two polymorphisms in putative transcriptional factor-binding sites. The CYP2C19*1, *2, *3, *4, *17, *23, *24 and *25 alleles have frequencies of 67.5, 25.5, 2, 0.5, 3, 0.5, 0.5 and 0.5%, respectively. Based on computational predictions, three novel alleles (CYP2C19*23, *24 and *25) are deleterious mutations of the CYP2C19 protein. In CYP2D6, we identified 84 different polymorphisms, including 18 novel single-nucleotide polymorphisms. One novel polymorphism is located in a potential cis-regulatory element of the gene. The allele frequencies of CYP2D6*1, *2, *4, *5, *6, *10, *14, *21, *36, *41, *43, *52 and *71 are 18.5, 14, 1, 7, 0.5, 49, 1.5, 0.5, 1, 4, 0.5, 1 and 1.5%, respectively. The occurrence of CYP2D6 duplication is 0.5%. The novel CYP2D6*71 is anticipated as a putative poor metabolizer allele. We also performed linkage disequilibrium analysis and observed strong linkage disequilibrium spanning of the CYP2C19 and CYP2D6 regions. In addition, network analysis showed that 15 haplotypes of CYP2C19 and 22 of CYP2D6 are classified into five and three groups, respectively. Comparisons of allele frequency distributions revealed significant interethnic and intraethnic differences in these two genes. In conclusion, this study revealed that CYP2C19 and CYP2D6 have a complicated allele composition and distinct frequency distribution in Han Chinese.

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Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: A cross-ethnic comparative study

Cited by 102 publications

References 25 publications

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

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

Cytochrome P450 2C19 loss-of-function polymorphism is associated with an increased treatment-related mortality in patients undergoing allogeneic transplantation

Genetic polymorphism, linkage disequilibrium, haplotype structure and novel allele analysis of CYP2C19 and CYP2D6 in Han Chinese

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