Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Novel Cyp2C19 Genetic Variants associated with Stent Thrombosis: a Next Generation Sequencing Study
Mayo Clinic, Rochester, MN, USA.
Mayo Clinic, Rochester, MN, USA.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Show others and affiliations
2018 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 71, no 11, p. 1205-1205Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background

Commonly tested Loss-of-function (LOF) alleles in CYP2C19 are present in 30-40% of patients who experience stent thrombosis. The objective of this study was to identify novel genetic variants in CYP2C19 gene associated with stent thrombosis.

Methods

We included 70 patients with definite stent thrombosis while on clopidogrel who had stored DNA samples in our institutional (n=12) or PLATO trial (n=70) biorepository. Cases were matched 1:1 with controls for age, race, sex, diabetes, type of stent, and presentation. All controls were on clopidogrel and free of recurrent events. Clinical Pharmacogenetics (PGx) Implementation Consortium (CPIC) guidelines were used to determine the list of known PGx variants and dbSNP version 142 was used to assess novel variants. Whole exome sequencing was performed using the protocol for Agilent's SureSelect Human All Exon v5 + UTRs 75 MB kit and additional custom primers were designed to cover the entire CYP2C19 gene.

Results

Mean age was 63 ± 12 years, and 71% were male. We identified a total of 456 single nucleotide variants (SNV) in the CYP2C19 gene (cases: 376; controls: 288), of which 5 were synonymous, 6 non-synonymous, 46 indels and 449 intronic SNVs. There were 168 vs. 80 novel CYP2C19 variants and 10 vs. 5 indels in cases vs. controls, respectively. Four SNVs (3 missense and 1 synonymous) were present only in cases, whereas 3 SNVs (1 misssense, 1 synonymous and 1 intron) were unique to controls. There were no detectable differences in the frequency of LOF CYP2C19*2 allele (cases 34% vs. controls 31%) or other CPIC annotated PGx variants in cases and controls. After excluding the known PGx variants, there were 10 indels (all intronic) out of which 7 were novel in cases and were not present in controls.

Conclusion

We describe several novel genetic variants in the CYP2C19 gene in patients treated with clopidogrel after coronary stenting. We identified 168 novel SNVs and 10 novel indels in the CYP2C19 gene of patients with stent thrombosis. Four SNVs and 9 indels were unique to cases. Functional validation of these CYP2C19 genetic variants may provide important insights of CYP2C19 and the pathophysiology of stent thrombosis in clopidogrel treated patients.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC , 2018. Vol. 71, no 11, p. 1205-1205
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-357331DOI: 10.1016/S0735-1097(18)31746-7ISI: 000429659702455OAI: oai:DiVA.org:uu-357331DiVA, id: diva2:1239383
Conference
67th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), MAR 10-12, 2018, Orlando, FL
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full text

Search in DiVA

By author/editor
Åkerblom, AxelEriksson, NiclasWallentin, Lars
By organisation
CardiologyUCR-Uppsala Clinical Research Center
In the same journal
Journal of the American College of Cardiology
Cardiac and Cardiovascular Systems

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 8 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf