Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
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.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.gene.2021.145592 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!