Molecular heterogeneity at the CYP2D gene locus in Nicaraguans: impact of gene-flow from Europe

Agúndez, José A.G.; Ramírez, Rafael Robina; Hernández, Máximo; LLerena, Adrián; Benı́tez, Julio

doi:10.1097/00008571-199708000-00010

Cited by 23 publications

(20 citation statements)

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“…The frequency of genotypes with duplication/multiplication of active CYP2D6 alleles in Tepehuano subjects was the closest to those reported in Mexican Mestizos (7%) and white European populations (3-5%) [41] but higher than those for South American and Amerindian populations (0-1%) [9,10,32,45].…”

Section: Discussionmentioning

confidence: 48%

“…We identified a low frequency of non functional CYP2D6 alleles in the indigenous groups studied, with the exception of the CYP2D6*4 allele, which was found with a relatively high frequency in Seris (21.05%), similar to that in the Ngawbe (17.1%) and Embera (14.0%) groups of Panama and Colombia, Mexican Mestizos (13.1-11.2%), and other indigenous groups from Mexico (1.2%-7.3%) SupplemenTary Table 1 (see www.futuremedicine.com/doi/suppl/10.2217/pgs.13.203) [9,10,[15][16][17][25][26][27][28][29][30][31][32][33]. The CYP2D6*4 allele is of clinical significance and often causes altered drug clearance and drug response accounting for 97% of all the PM phenotypes in Caucasians [11].…”

Section: Discussionmentioning

confidence: 67%

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CYP2D6 Gene Polymorphisms and Predicted Phenotypes in Eight Indigenous Groups from Northwestern Mexico

et al. 2014

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Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 67%

CYP2D6 Gene Polymorphisms and Predicted Phenotypes in Eight Indigenous Groups from Northwestern Mexico

et al. 2014

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“…There are only two reports in the literature describing lack of 100T on CYP2D6*4. In one study, a single Basque individual lacked 100T on a CYP2D6*4 allele (Fuselli et al, 2004), whereas 17 of 40 (40%) and 16 of 62 (26%) CYP2D6*4 in Nicaraguans and Spanish subjects, respectively, lacked this SNP (Agundez et al, 1997). The family of our case, however, reported German and English origins and is unaware of any Spanish or Hispanic ancestors.…”

Section: Discussionmentioning

confidence: 61%

CYP2D636GENE ARRANGEMENTS WITHIN THECYP2D6LOCUS: ASSOCIATION OFCYP2D636WITH POOR METABOLIZER STATUS

Gaedigk

Bradford²,

Alander³

et al. 2006

Drug Metab Dispos

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ABSTRACT:Unexplained cases of CYP2D6 genotype/phenotype discordance continue to be discovered. In previous studies, several African Americans with a poor metabolizer phenotype carried the reduced function CYP2D6*10 allele in combination with a nonfunctional allele. We pursued the possibility that these alleles harbor either a known sequence variation (i.e., CYP2D6*36 carrying a gene conversion in exon 9 along the CYP2D6*10-defining 100C>T singlenucleotide polymorphism) or novel sequences variation(s). Discordant cases were evaluated by long-range polymerase chain reaction (PCR) to test for gene rearrangement events, and a 6.6-kilobase pair PCR product encompassing the CYP2D6 gene was cloned and entirely sequenced. Thereafter, allele frequencies were determined in different study populations comprising whites, African Americans, and Asians. Analyses covering the CYP2D7 to 2D6 gene region established that CYP2D6*36 did not only exist as a gene duplication (CYP2D6*36x2) or in tandem with *10 (CYP2D6*36؉*10), as previously reported, but also by itself. This "single" CYP2D6*36 allele was found in nine African Americans and one Asian, but was absent in the whites tested. Ultimately, the presence of CYP2D6*36 resolved genotype/phenotype discordance in three cases. We also discovered an exon 9 conversion-positive CYP2D6*4 gene in a duplication arrangement (CYP2D6*4Nx2) and a CYP2D6*4 allele lacking 100C>T (CYP2D6*4M) in two white subjects. The discovery of an allele that carries only one CYP2D6*36 gene copy provides unequivocal evidence that both CYP2D6*36 and *36x2 are associated with a poor metabolizer phenotype. Given a combined frequency of between 0.5 and 3% in African Americans and Asians, genotyping for CYP2D6*36 should improve the accuracy of genotypebased phenotype prediction in these populations.

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“…One hundred twelve healthy unrelated Mestizo subjects between 16 For CYP2D6 genotyping, 5-ml blood samples had previously been collected in ethylenediamine tetraacetic acid tubes, and DNA was extracted using the QIAamp DNA blood kit (Qiagen, Hilden, Germany). The CYP2D6 genotype for the * 5 allele and gene multiplications was determined by long-range PCR [11] .…”

Section: Subjectsmentioning

confidence: 99%

Influence of CYP2D6 Deletion, Multiplication, –1584C→G, 31G→A and 2988G→A Gene Polymorphisms on Dextromethorphan Metabolism among Mexican Tepehuanos and Mestizos

et al. 2010

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The aim of this study was to explain the variability of CYP2D6 activity by the identification of CYP2D6 deletion and multiplications, and the single-nucleotide polymorphisms (SNPs) –1584C→G, 31G→A and 2988G→A in Mexican Mestizo and Tepehuano subjects. One hundred twelve Mestizos and 99 Tepehuano Amerindians were studied, who were previously phenotyped with dextromethorphan. The frequencies of CYP2D6*2A [–1584C→G] and *35 [–1584C→G, 31G→A] were 10.7 and 4.1%, respectively, in Mestizos, which is evidently a trend towards an extensive metabolism in carriers of the –1584G change. In Tepehuanos, *2A was identified with a frequency of 20%, and the allele *35 was not found. The frequencies of CYP2D6*5 (deletion) and *41[2988G→A] were 1.3 and 2.2% in Mestizos and 0.5 and 1% in Tepehuanos, respectively. The SNP 2988A was found to be significantly related with the intermediate metabolizer phenotype in Mestizos (R = 0.309; n = 88; p = 0.006). The multiplications had frequencies of 4.1% in Mestizos and 1.5% in Tepehuanos. Only in the Mestizos did the presence of multiplications significantly decrease the DM/DX (dextromethorphan/dextrorphan) values (R = 0.273; n = 88; p = 0.016). The polymorphisms studied had different frequencies between Tepehuanos and Mestizos (p < 0.001); however, in the Tepehuano group these had a low influence on their phenotypic expression. It helps to understand the genotype-phenotype relationships of CYP2D6 in our studied populations.

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Molecular heterogeneity at the CYP2D gene locus in Nicaraguans: impact of gene-flow from Europe

Cited by 23 publications

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CYP2D6 Gene Polymorphisms and Predicted Phenotypes in Eight Indigenous Groups from Northwestern Mexico

CYP2D6 Gene Polymorphisms and Predicted Phenotypes in Eight Indigenous Groups from Northwestern Mexico

CYP2D636GENE ARRANGEMENTS WITHIN THECYP2D6LOCUS: ASSOCIATION OFCYP2D636WITH POOR METABOLIZER STATUS

Influence of <i>CYP2D6</i> Deletion, Multiplication, <i>–1584C</i>→<i>G</i>, <i>31G</i>→<i>A</i> and <i>2988G</i>→<i>A</i> Gene Polymorphisms on Dextromethorphan Metabolism among Mexican Tepehuanos and Mestizos

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Molecular heterogeneity at the CYP2D gene locus in Nicaraguans: impact of gene-flow from Europe

Cited by 23 publications

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CYP2D6 Gene Polymorphisms and Predicted Phenotypes in Eight Indigenous Groups from Northwestern Mexico

CYP2D6 Gene Polymorphisms and Predicted Phenotypes in Eight Indigenous Groups from Northwestern Mexico

CYP2D6*36GENE ARRANGEMENTS WITHIN THECYP2D6LOCUS: ASSOCIATION OFCYP2D6*36WITH POOR METABOLIZER STATUS

Influence of <i>CYP2D6</i> Deletion, Multiplication, <i>–1584C</i>→<i>G</i>, <i>31G</i>→<i>A</i> and <i>2988G</i>→<i>A</i> Gene Polymorphisms on Dextromethorphan Metabolism among Mexican Tepehuanos and Mestizos

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CYP2D636GENE ARRANGEMENTS WITHIN THECYP2D6LOCUS: ASSOCIATION OFCYP2D636WITH POOR METABOLIZER STATUS