Umeå universitets logga

umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
To Modify or Not to Modify: Allele-Specific Effects of 3’UTR-KCNQ1 Single Nucleotide Polymorphisms on Clinical Phenotype in a Long QT 1 Founder Population Segregating a Dominant-Negative Mutation
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Department of Physiology, University of Auckland, Auckland, New Zealand.ORCID-id: 0000-0002-9323-3166
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.ORCID-id: 0000-0002-1811-225X
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.ORCID-id: 0000-0002-7766-8557
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.ORCID-id: 0000-0001-5275-2544
Visa övriga samt affilieringar
2022 (Engelska)Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 11, nr 18, artikel-id e025981Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND: There are conflicting reports with regard to the allele-specific gene suppression effects of single nucleotide polymorphisms (SNPs) in the 3’untranslated region (3’UTR) of the KCNQ1 gene in long QT syndrome type 1 (LQT1) populations. Here we assess the allele-specific effects of 3 previously published 3’UTR-KCNQ1’s SNPs in a LQT1 founder population segregating a dominant-negative mutation.

METHODS AND RESULTS: Bidirectional sequencing of the KCNQ1’s 3’UTR was performed in the p.Y111C founder population (n=232, 147 genotype positive), with a minor allele frequency of 0.1 for SNP1 (rs2519184) and 0.6 for linked SNP2 (rs8234) and SNP3 (rs107980). Allelic phase was assessed in trios aided by haplotype data, revealing a high prevalence of derived SNP2/3 in cis with p.Y111C (89%). Allele-specific association analyses, corrected using a relatedness matrix, were performed between 3’UTR-KCNQ1 SNP genotypes and clinical phenotypes. SNP1 in trans was associated with a significantly higher proportion of symptomatic phenotype compared with no derived SNP1 allele in trans (58% versus 32%, corrected P=0.027). SNP2/3 in cis was associated with a significantly lower proportion of symptomatic phenotype compared with no derived SNP2/3 allele in cis (32% versus 69%, corrected P=0.010).

CONCLUSIONS: Allele-specific modifying effects on symptomatic phenotype of 3’UTR-KCNQ1 SNPs rs2519184, rs8234, and rs107980 were seen in a LQT1 founder population segregating a dominant-negative mutation. The high prevalence of sup-pressive 3’UTR-KCNQ1 SNPs segregating with the founder mutation could contribute to the previously documented low incidence of cardiac events in heterozygous carriers of the p.Y111C KCNQ1 mutation.

Ort, förlag, år, upplaga, sidor
American Heart Association , 2022. Vol. 11, nr 18, artikel-id e025981
Nyckelord [en]
arrhythmia and electrophysiology, molecular cardiology
Nationell ämneskategori
Medicinsk genetik Kardiologi
Forskningsämne
genetik
Identifikatorer
URN: urn:nbn:se:umu:diva-199893DOI: 10.1161/JAHA.122.025981ISI: 000858504900049PubMedID: 36102229Scopus ID: 2-s2.0-85138386692OAI: oai:DiVA.org:umu-199893DiVA, id: diva2:1700703
Forskningsfinansiär
Hjärt-LungfondenTillgänglig från: 2022-10-03 Skapad: 2022-10-03 Senast uppdaterad: 2023-09-05Bibliografiskt granskad

Open Access i DiVA

fulltext(2209 kB)73 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 2209 kBChecksumma SHA-512
75c4833e4141f7c998397bec40e27e4a592aee7009fc7eebd3956a06935d9606b37f00e499622c92dfaff97fe666437464050caf847931173871517c2da06f63
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMedScopus

Person

Winbo, AnnikaDiamant, Ulla-BrittPersson, JohanJensen, Steen M.Rydberg, Annika

Sök vidare i DiVA

Av författaren/redaktören
Winbo, AnnikaDiamant, Ulla-BrittPersson, JohanJensen, Steen M.Rydberg, Annika
Av organisationen
PediatrikKardiologi
I samma tidskrift
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Medicinsk genetikKardiologi

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 73 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 201 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf