Copy number variation profiling in pharmacogenetics CYP-450 and GST genes in Colombian population

Background: Copy Number variation (CNVs) in genes related to drug absorption, distribution, metabolism and excretion (ADME) are relevant in the interindividual variability of drug response. Studies of the CNVs in ADME genes in Latin America population are lacking. The objective of the study was to identify the genetic variability of CNVs in CYP-450 and GST genes in a subgroup of individuals of Colombian origin. Methods: Genomic DNA was isolated from 123 healthy individuals from a Colombian population. Multiplex Ligation-Dependent Probe Amplification (MLPA) was performed for the identification of CNVs in 40 genomic regions of 11 CYP-450 and 3 GST genes. The genetic variability, allelic and genotypic frequencies were analyzed. Results: We found that 13 out of 14 genes had CNVs: 5 (35.7%) exhibited deletions and duplications, while 8 (57.1%) presented either deletions or duplications. 33.3% of individuals carried deletions and duplications while 49.6% had a unique type of CNV (deletion or duplication). The allelic frequencies of the CYP and GST genes were 0 to 47.6% (allele null), 0 to 17.5% (duplicated alleles) and 37 to 100% (normal alleles). Conclusions: Our results describe, for the first time, the genomic profile of CNVs in a subgroup of Colombian population in GST and CYP-450 genes. GST genes indicated greater genetic variability than CYP-450 genes. The data obtained contributes to the knowledge of genetic profiles in Latin American subgroups. Although the clinical relevance of CNVs has not been fully established, it is a valuable source of pharmacogenetic variability data with potential involvement in the response to medications. © 2019 The Author(s).

• Fecha de publicación: 2019
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/23573
• Acceso en línea: https://doi.org/10.1186/s12920-019-0556-x; https://repository.urosario.edu.co/handle/10336/23573
• Palabra clave: Genomic DNA; Cytochrome P450; Glutathione transferase; Adult; Allele; Article; Cohort analysis; Colombian; Copy number variation; CYP-450 gene; CYP1A1 gene; CYP1A2 gene; CYP1B1 gene; CYP2A6 gene; CYP2B6 gene; CYP2C19 gene; CYP2C9 gene; CYP2D gene; CYP2E1 gene; CYP3A4 gene; CYP3A5 gene; DNA isolation; Female; Gene; Gene deletion; Gene duplication; Gene frequency; Genetic profile; Genetic variability; Genotype; GST gene; GSTM1 gene; GSTP1 gene; GSTT1 gene; Human; Male; Normal human; Personalized medicine; Pharmacogenetics; Priority journal; South and Central America; Colombia; Genetics; Colombia; Cytochrome P-450 Enzyme System; DNA Copy Number Variations; Gene Frequency; Genotype; Glutathione Transferase; Humans; Pharmacogenetics; Allele frequency; DNA copy number variation; Personalized medicine; DNA; Pharmacogenomics
• License: Abierto (Texto Completo)