Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population

Vargas‐Alarcón, Gilberto; Ramírez‐Bello, Julián; Peña, Aurora de la; Calderón-Cruz, Beatriz; Peña‐Duque, Marco Antonio; Martínez-Ríos, Marco Antonio; Ramírez-Fuentes, Silvestre; Pérez-Méndez, Óscar; Fragoso, José Manuel

doi:10.1007/s11033-014-3590-y

Cited by 18 publications

(7 citation statements)

References 34 publications

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“…38 The frequency of ABCB1 3435C4T in the MM population studied here is similar to that found in previous reports. 39,40 Also comparable with our results were the frequencies of the three ABCB1 polymorphisms reported among individuals with Mexican ancestry living in Los Angeles, California (ABCB1 1236C = 0.540, 2677G = 0.570 and 3435C = 0.540; data from HapMap project consulted in NCBI dbSNP). 41 All patients included in this study were currently treated with PHT and 61% had co-administration of at least one more drug, including antiepileptics reported to reduce or enhance PHT plasma concentrations.…”

Section: Discussionsupporting

confidence: 88%

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

et al. 2015

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We aimed to explore the possible influence of CYP2C9 (*2, *3 and IVS8-109 A>T), CYP2C19 (*2, *3 and *17) and ABCB1 (1236C>T, 2677G>A/T and 3435C>T) on phenytoin (PHT) plasma concentrations in 64 Mexican Mestizo (MM) patients with epilepsy currently treated with PHT in mono- (n=25) and polytherapy (n=39). Genotype and allele frequencies of these variants were also estimated in 300 MM healthy volunteers. Linear regression models were used to assess associations between the dependent variables (PHT plasma concentration and dose-corrected PHT concentration) with independent variables (CYP2C9, CYP2C19 and ABCB1 genotypes, ABCB1 haplotypes, age, sex, weight, and polytherapy). In multivariate models, CYP2C9 IVS8-109 T was significantly associated with higher PHT plasma concentrations (t(64)=2.27; P=0.03). Moreover, this allele was more frequent in the supratherapeutic group as compared with the subtherapeutic group (0.13 versus 0.03, respectively; P=0.05, Fisher's exact test). Results suggest that CYP2C9 IVS8-109 T allele may decrease CYP2C9 enzymatic activity on PHT. More research is needed to confirm findings.

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Section: Discussionsupporting

confidence: 88%

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

et al. 2015

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“…Here, we hypothesize that Natives will show a lower probability of impaired CYP2C9 activity compared to Mestizos and both of them lower to CEU. These comparisons have been previously confirmed for CYP2C9 , ABCB1 , CYP3A5 , and CYP2C19 (Vargas-Alarcón et al, 2014; Zhou et al, 2017). For CYP2C19 , we can infer that a higher proportion of Natives are normal/extensive metabolizers.…”

Section: Discussionsupporting

confidence: 67%

Variation in Actionable Pharmacogenetic Markers in Natives and Mestizos From Mexico

et al. 2019

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The identification and characterization of pharmacogenetic variants in Latin American populations is still an ongoing endeavor. Here, we investigated SNVs on genes listed by the Pharmacogenomics Knowledge Base in 1284 Mestizos and 94 Natives from Mexico. Five institutional cohorts with NGS data were retrieved from different research projects at INMEGEN, sequencing files were filtered for 55 pharmacogenes present in all cohorts to identify novel and known variation. Bioinformatic tools VEP, PROVEAN, and FATHMM were used to assess, in silico, the functional impact of this variation. Next, we focused on 17 genes with actionable variants that have been clinically implemented. Allele frequencies were compared with major continental groups and differences discussed in the scope of a pharmacogenomic impact. We observed a wide genetic variability for known and novel SNVs, the largest variation was on UGT1A > ACE > COMT > ABCB1 and the lowest on APOE and NAT2. Although with allele frequencies around 1%, novel variation was observed in 16 of 17 PGKB genes. In Natives we identified 59 variants and 58 in Mestizos. Several genes did not show novel variation, on CYP2B6, CYP2D6, and CYP3A4 in Natives; and APOE, UGT1A, and VKORC1 in Mestizos. Similarities in allele frequency, comparing major continental groups for VIP pharmacogenes, hint towards a comparable PGx for drugs metabolized by UGT1A1, DPYD, ABCB1, CBR3, COMT, and TPMT; in contrast to variants on CYP3A5 and CYP2B6 for which significant MAF differences were identified. Our observations offer some discernment into the extent of pharmacogenetic variation registered up-to-date in Mexicans and contribute to quantitatively dissect actionable pharmacogenetic variants in Natives and Mestizos.

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“…In the present study, the P2Y12 gene haplotype frequency of H2 was 8.6% in the Shandong Han population, which was lower than that in Caucasians (13.8%) and Mexican Mestizos (12.8%) 3,21. This result may be related to racial differences.…”

Section: Discussioncontrasting

confidence: 65%

Platelet membrane receptor P2Y12 H1/H2 polymorphisms is highly associated with cerebral infarction: a case-control study

Lu¹,

Zhou²,

Zheng³

et al. 2018

NDT

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ObjectivesThis study aimed to determine the relationship between the polymorphisms of the H1/H2 gene of platelet membrane receptor P2Y12 and cerebral infarction (CI) in a Han population in North Shandong Province, People’s Republic of China.Patients and methodsA case–control study, which involved 168 nonstoke subjects (contrast group) and 152 CI patients (CI group), was conducted. The state of subjects in the CI group was validated by computed tomography or MRI. The clinical data were categorized into two groups. The data included age, gender, smoking, drinking, shrinkage pressure, diastolic blood pressure, blood glucose, cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, serum uric acid, fibrinogen and homocysteine. The polymorphisms were genotyped with PCR and restriction fragment length polymorphism analysis. The distribution characteristics of nonstoke subjects and CI patients and the relationship between the polymorphisms of the H1/H2 gene of platelet membrane receptor P2Y12 and ischemic stroke were analyzed.ResultsNo significant difference was found between the contrast group and CI group (P>0.05) in terms of age, gender composition, smoking, alcohol consumption, blood glucose, cholesterol, triglyceride, low-density protein, high-density lipoprotein cholesterol, uric acid and homocysteine. In contrast, significant differences were found between these two groups (P<0.01) in terms of SBP, DBP and plasma fibrinogen level. The genotyping revealed 112 carriers of the wild-type H1/H1 genotype and 40 carriers of the mutational H2 allele of P2Y12 H1/H2 in the CI group and 140 carriers of the wild-type H1/H1 genotype and 28 carriers of the mutational H2 allele of P2Y12 H1/H2 in the contrast group. Furthermore, the H1/H2 and H2/H2 gene frequencies (26.3%) were significantly higher in the CI group (χ2=4.440, P<0.05) than those in the contrast group (16.7%). Moreover, the frequencies of the H2 allele in the CI and contrast groups were 14.5% and 8.6%, respectively, and the difference was statistically significant (χ2=5.392, P<0.05). Multiple logistic regression analysis results revealed that factors associated with CI include systolic blood pressure and plasma fibrinogen level, which carry the −893T gene. After adjusting for potential confounding factors, the H2 allele carriers had a 1.928-fold increased risk for CI (OR=1.928, 95% confidence interval: 1.137–3.188; P=0.038) when compared with noncarriers.ConclusionThe present study found that hypertension and elevated plasma fibrinogen levels are significant risk factors for ischemic stroke and confirmed that the H1/H2 and H2/H2 genes of platelet membrane glycoprotein receptor P2Y12 are risk factors of ischemic stroke.

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Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population

Cited by 18 publications

References 34 publications

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

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

Variation in Actionable Pharmacogenetic Markers in Natives and Mestizos From Mexico

Platelet membrane receptor P2Y12 H1/H2 polymorphisms is highly associated with cerebral infarction: a case-control study

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