Analysis of <i>CYP2D6</i> Allele Frequencies and Identification of Novel SNPs and Sequence Variations in Sardinians

Falzoi, Matteo; Pira, Luigi; Lazzari, Paolo; Pani, Luca

doi:10.5402/2013/204560

Cited by 5 publications

(21 citation statements)

References 19 publications

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“…The 69 polymorphisms analyzed in this study were selected using principal SNP web databases such as the Human CYP Allele Nomenclature Committee [7] and the NCBI Single Nucleotide Polymorphism dbSNP [8] websites. Selection criteria depended mainly on the pharmacogenetic effects described for every allele in the Caucasian population [5,7,[9][10][11][12][13][14][15][16]. Not all selected SNPs are involved in aminoacidic or transcriptional variation ( Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…The 5 10-mer tag was added to PCR primers, in order to improve PCR efficiency. Name 5 10-mer tag 5 -Sequence-3 Direction From -1780 to -1758 P-1780 [5 [5]. Forward primer (P-1780, Table 2) was designed in a highly nonhomologous CYP2D6/CYP2D7P/CYP2D8P 5 untranslated region [5].…”

Section: Methodsmentioning

confidence: 99%

“…A = alanine; R = arginine; N = asparagine; D = aspartic acid; C = cysteine; E = glutamic acide; Q = glutamine; G = glycine; H = histidine; I = isoleucine; L = leucine; K = lysine; M = methionine; F = phenylalanine; P = proline; S = serine; T = threonine; W = tryptophan; Y = tyrosine; V = valine. In bold characters newly discovered SNPs in [5,17,18,21].…”

Section: Cyp2d6 Snpsmentioning

confidence: 99%

“…The genotyping of the CYP2D6 gene was difficult due to its polymorphic nature, the presence of two flanking pseudogenes and copy number variants. To avoid false genotyping, resulting from nonspecific coamplification of the highly homologous pseudogenes, we developed the analysis of this gene in another way by using long PCR protocol coupled with single allele analysis and followed by sequencing [5]. In this work, we aimed to create a CYP2D6 medium-throughput SNPs screening platform using the Sequenom (CA, USA) matrix-assisted 997C>G -1039C>T -1513C>T -1659G>A V 1 3 6 I 1661G>C -1704C>G Q151E 1707delT Frameshift 1724C>T -1749A>G N 1 6 6 D 1757C>T -1758G>A G 1 6 9 R 1758G>T G 1 6 9 X 1846G>A Splicing defect 1863 1864insTTTCGCCCC 174 175insFRP 1869T>C -1943G>A R 2 0 1 H 1979T>C -2291G>A -2483G>T A 2 3 7 S 2539 2542delAACT Frameshift 2549delA Frameshift 2575C>A -2587 2590delGACT Frameshift 2615 2617delAAG K281del 2850C>T R 2 9 6 C Table 1: Continued.…”

Section: Introductionmentioning

confidence: 99%

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Genotyping of CYP2D6 Polymorphisms by MALDI-TOF Mass Spectrometry in Sardinian People

et al. 2013

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The CYP2D6 enzyme is involved in the metabolism of many commonly prescribed drugs. The presence of CYP2D6 gene SNPs can alter CYP2D6 enzymatic activity with effects ranging considerably within a population. Objectives. In this study, we have developed a genotyping platform able to determine the alleles related to interindividual variability in the CYP2D6 gene. Design and Methods. We used a long PCR strategy coupled to MALDI-TOF mass spectrometry (Sequenom) to develop a SNPs genotyping method. Furthermore, an amplification allele specific was carried out to infer the correct allelic phase. Results. We tested the multiplex platform in 250 DNA Sardinian samples and found it to be 100% concordant with the sequencing results of our previous work. Conclusions. The MALDI-TOF-based multiplexing system allowed simultaneous and efficient genotyping of a set of CYP2D6 SNPs, evidencing its potential use in diagnostic test development to predict drug responses and clinical outcomes.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Cyp2d6 Snpsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genotyping of CYP2D6 Polymorphisms by MALDI-TOF Mass Spectrometry in Sardinian People

et al. 2013

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“…Furthermore, because it was reported that there are differences in allelic distributions in populations of different ethnic group and geographic areas [30, 31], we first determined the CYP2C9 , CYP2C19, and CYP2D6 genotype profile of our 100 individuals from Salento, a Southern Italy region. A total of 12 different variant alleles were identified in the study population.…”

Section: Discussionmentioning

confidence: 99%

Assessment of CYP2C9, CYP2C19, and CYP2D6 Polymorphisms in Allergic Patients with Chemical Sensitivity

D'Attis

Massari

Mazzei

et al. 2019

Int Arch Allergy Immunol

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Background: Self-reported chemical sensitivity (SCS) is characterized by adverse effects due to exposure to low levels of chemical substances. The clinical manifestations of SCS are similar to the allergy, and a high percentage of individuals with both diseases have been found. Various genes, especially genes of importance to the metabolism of xenobiotic compounds, have been associated with SCS. Objectives: The purpose of this study was to investigate whether allergic individuals with chemical sensitivity differed from allergic patients without chemical sensitivity with regard to the distribution of genotype and phenotype of CYP2C9, CYP2C19, and CYP2D6 polymorphisms. Methods: A total of 180 patients were enrolled for this study. A questionnaire was employed to collect information on individual chemical sensitivity, while the Skin prick test and the PATCH test were used to verify the presence of an allergic condition against inhalants or contact allergens, respectively. For the evaluation of the CYP2C9, CYP2C19, and CYP2D6 polymorphisms, we used a strategy based on the amplification of the entire gene coupled to direct genomic DNA sequencing analysis. Results: Overall, a total of 15 different CYP2C9, CYP2C19, and CYP2D6 haplotypes were identified in our population. If the 5 CYP2C9 and the 2 CYP2C19 identified alleles correspond to the previously described ones, 4 of the 8 CYP2D6 haplotypes, detected in the study group, present new SNPs combinations. These new suballeles were categorized as CYP2D6*2M Salento Variant 1, CYP2D6*35B Salento Variant 2, CYP2D6*41 Salento Variant 3, and CYP2D6*4P Salento Variant 4 due to the presence of the key SNPs 2,850 C>T, 31G>A, 2,988 G>A, and 1,846 G>A, respectively. When the allergic individuals are divided into 2 groups according to their SCS score, we observed that the distribution of the CYP2D6 phenotypes was significantly different between the 2 groups. Conclusions: Our idea is that the application of the questionnaire that we have adopted has enabled us to diagnose a degree of chemical sensitivity, which results as comorbid of the allergic disease and in which a condition of poor or intermediate metabolizes for the detrimental CYP2D6 alleles, could represent a discriminant between the chemical sensitivity and the health state.

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Distribution of CYP2D6 genotypes in the Indian population – preliminary report

Paradkar

Dherai

Shetty

et al. 2018

Drug Metabolism and Personalized Therapy

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Background Cytochrome P450 2D6 (CYP2D6) allelic distribution exhibits differences amongst worldwide populations. There is lack of data from Mumbai, Western India, on the major CYP2D6 alleles *2, *3, *4, *5, *10 and *41, and gene multiplication alleles. Hence, the present study was undertaken to determine the distribution of these clinically relevant CYP2D6 alleles. Methods Fifty-two healthy individuals were screened using TaqMan SNP genotyping and copy number variation (CNV) assays by real-time polymerase chain reaction. Results The allele frequencies of CYP2D6*2, *3, *4, *5, *10 and *41 alleles were observed to be 30.8%, 0%, 11.5%, 3.9%, 19.2% and 17.3%, respectively. The frequency of CYP2D6 gene one copy, two copies, three copies and four copies were observed to be 7.7%, 76.9%, 13.5% and 1.9%, respectively. The predicted phenotype frequency was observed to be 78.9%, 3.9% and 9.6% for extensive, intermediate, and ultrarapid metabolizers, respectively, whereas poor metabolizers were not detected. Conclusions CYP2D6 allele frequencies showed heterogeneous distribution in the present study as compared to worldwide populations. High frequency of CYP2D6*41 allele, gene duplication alleles and UMs was observed. The scarcity and/or lack of data from the Indian population on these alleles further substantiates the need for screening of CYP2D6 genotyping.

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Analysis of CYP2D6 Allele Frequencies and Identification of Novel SNPs and Sequence Variations in Sardinians

Cited by 5 publications

References 19 publications

Genotyping of CYP2D6 Polymorphisms by MALDI-TOF Mass Spectrometry in Sardinian People

Genotyping of CYP2D6 Polymorphisms by MALDI-TOF Mass Spectrometry in Sardinian People

Assessment of CYP2C9, CYP2C19, and CYP2D6 Polymorphisms in Allergic Patients with Chemical Sensitivity

Distribution of CYP2D6 genotypes in the Indian population – preliminary report

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