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Mechanistic insights into the CYP2C19 genetic variants prevalent in the Indian population. | LitMetric

AI Article Synopsis

  • This study focuses on the CYP2C19 gene, which affects how some drugs work in the body, specifically in a sample of 2000 healthy Indians.
  • Researchers identified five common variants of CYP2C19, with *2 and *17 being the most prevalent, impacting drug metabolism.
  • The findings suggest that *2 and *3 are less effective for drug metabolism (loss-of-function), while *17 enhances drug action (gain-of-function), indicating their significance for personalized medicine in this population.

Article Abstract

Purpose: CYP2C19 metabolizes the antiplatelet and antiepileptic drugs. Any alteration in CYP2C19 activity might influence the therapeutic efficacy. The objective of this study was to identify CYP2C19 variants prevalent in Indians and perform their in silico characterization.

Methods: Infinium global screening array (GSA) was used for CYP2C19 genotyping in 2000 healthy Indians. In addition, we performed in silico characterization of the identified variants.

Results: Out of the 11 variants covered (*2, *3, *4,*5,*6, *7,*8, *9,*10,*11, and *17), five were identified in Indians (*2, *3, *6,*8 and *17). The *2 and *17 were the most prevalent alleles (minor allele frequencies, MAF: 32.0% and 13.95%). The *3, *6 and *8 were rare (MAFs: 0.425%, 0.025% and 0.05%). The *2 variant is shown to affect the splicing at the fifth exon-intron boundary. The *3 variant is a non-sense variant that is predicted to be deleterious. On the otherhand, the *17 variant showed more binding affinity for GATA binding protein 1 (GATA1), myocyte enhancer factor 2 (MEF2) and ectotropic viral integration site 1 (EVI1). The *6 and *8 variants predicted to be deleterious. The *2, *3 and *7 variants showed lesser probability of exon skipping, while *17 showed more probability. The genotype distribution of Indian subjects is comparable with that of South Asians (SAS) (1000 genome project, phase 3).

Conclusion: The *2, *3 and *17 variants are the key pharmacogenetic determinants in Indians. The *2 and *3 are loss-of-function variants. The *17 is a gain-of-function variant with increased binding of transcriptional factors.

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Source
http://dx.doi.org/10.1016/j.gene.2021.145592DOI Listing

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