Pharmacogenomic Assessment of Mexican and Peruvian populations

Marsh, Sharon; King, Cristi R.; Booven, Derek J. Van; Revollo, Jane Yen; Gilman, Robert H.; McLeod, Howard L.

doi:10.2217/pgs.15.10

Cited by 17 publications

(9 citation statements)

References 59 publications

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“…The overall impact of these differences cannot be conclusive, but it is relevant for many other drugs, for which its clearance rate is limited by UGT1A1. Our NGS data did not identify other key variants such as UGT1A1 *28 rs3064774 or rs4148323 which have been shown to be differently distributed in other Latin American countries (Marsh et al, 2015).…”

Section: Discussioncontrasting

confidence: 55%

“…Pharmacogenetic studies in Mexican populations have been directed towards the identification of markers previously reported with functional consequences for drug safety and efficacy (Contreras et al, 2011; Bonifaz-Pena et al, 2014; Marsh et al, 2015; Fricke-Galindo et al, 2016). The advent of faster and more accessible technologies has made feasible to investigate a broader swath of the pharmacogenome including the presence of novel variants.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Variation in Actionable Pharmacogenetic Markers in Natives and Mestizos From Mexico

et al. 2019

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“…The differences in the frequencies could be due to population stratification and/or sample size, among other variables. The admixture in the African–American population is about 10–20% from European genetic ancestry and the frequency differences observed between any two populations that have high admixture has been observed previously [25,26]. Allele frequency differences in admixed populations must be considered in studies performed in populations even within the same country [26].…”

Section: Discussionmentioning

confidence: 92%

Prevalence of Pain-Related Single Nucleotide Polymorphisms in Patients of African Origin with Sickle Cell Disease

et al. 2015

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Background Prospective pain genetics research is hindered by a lack of data on the prevalence of polymorphisms in pain-relevant genes for patients with sickle cell disease (SCD). For African–Americans in general, limited information is available in public databases. Methods We prioritized and examined the genotype and allele frequencies of 115 SNPs from 49 candidate pain genes in 199 adult African–Americans and pediatric patients of African origin with SCD. Analyses were performed and compared with available data from public databases. Results Genotype and allele frequencies of a number of SNPs were found to be different between our cohort and those from the databases and between adult and pediatric subjects. Conclusion As pain therapy is inadequate in a significant percentage of patients with SCD, candidate pain genetic studies may aid in designing precision pain medicine. We provide prevalence data as a reference for prospective genetic studies in this population.

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“…Hardy-Weinberg testing was not possible for DMET Plus because specific UGT1A1 genotypes are not reported (see Table 2 legend), as well as for genotyping platforms that were used to test certain genotype categories: fPCR and Pharmacoscan. Allele frequencies of UGT1A1*1 (i.e., (TA) 6 ) obtained by Illumina sequencing matched previously-reported data (p > 0.178) for Caucasians (wild-type allele frequency (*1; (TA) 6 ) = 0.76 vs. 0.70) [16], African Americans (wild-type allele frequency (*1; (TA) 6 ) = 0.38 vs. 0.50) [17], Hispanics (wild-type allele frequency (*1; (TA) 6 ) = 0.70 vs. 0.62) [18], and Asians (wild-type allele frequency (*1; (TA) 6 ) = 0.78 vs. 0.87) [16].…”

Section: Genotyping Resultsmentioning

confidence: 99%

Comparison of Eight Technologies to Determine Genotype at the UGT1A1 (TA)n Repeat Polymorphism: Potential Clinical Consequences of Genotyping Errors?

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et al. 2020

IJMS

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To ensure accuracy of UGT1A1 (TA)n (rs3064744) genotyping for use in pharmacogenomics-based irinotecan dosing, we tested the concordance of several commonly used genotyping technologies. Heuristic genotype groupings and principal component analysis demonstrated concordance for Illumina sequencing, fragment analysis, and fluorescent PCR. However, Illumina sequencing and fragment analysis returned a range of fragment sizes, likely arising due to PCR “slippage”. Direct sequencing was accurate, but this method led to ambiguous electrophoregrams, hampering interpretation of heterozygotes. Gel sizing, pyrosequencing, and array-based technologies were less concordant. Pharmacoscan genotyping was concordant, but it does not ascertain (TA)8 genotypes that are common in African populations. Method-based genotyping differences were also observed in the publication record (p < 0.0046), although fragment analysis and direct sequencing were concordant (p = 0.11). Genotyping errors can have significant consequences in a clinical setting. At the present time, we recommend that all genotyping for this allele be conducted with fluorescent PCR (fPCR).

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Pharmacogenomic Assessment of Mexican and Peruvian populations

Cited by 17 publications

References 59 publications

Variation in Actionable Pharmacogenetic Markers in Natives and Mestizos From Mexico

Variation in Actionable Pharmacogenetic Markers in Natives and Mestizos From Mexico

Prevalence of Pain-Related Single Nucleotide Polymorphisms in Patients of African Origin with Sickle Cell Disease

Comparison of Eight Technologies to Determine Genotype at the UGT1A1 (TA)n Repeat Polymorphism: Potential Clinical Consequences of Genotyping Errors?

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