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  • Meisgen, Sabrina (author)

The HLA locus contains novel foetal susceptibility alleles for congenital heart block with significant paternal influence

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • 2014-01-20
  • Wiley,2014
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-219521
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-219521URI
  • https://doi.org/10.1111/joim.12179DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:129224725URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • OBJECTIVE: The main aim of this study was to identify foetal susceptibility genes on chromosome six for Ro/SSA autoantibody-mediated congenital heart block.SUBJECTS AND DESIGN: Single nucleotide polymorphism (SNP) genotyping of individuals in the Swedish Congenital Heart Block (CHB) study population was performed. Low-resolution HLA-A, -Cw and -DRB1 allele typing was carried out in 86 families comprising 339 individuals (86 Ro/SSA autoantibody-positive mothers, 71 fathers, 87 CHB index cases, and 95 unaffected siblings).RESULTS: A case-control comparison between index cases and population-based out-of-study controls (n=1710) revealed association of CHB with 15 SNPs in the 6p21.3 MHC locus at a chromosome-wide significance of p<2.59×10(-6) (OR 2.21-3.12). In a family-based analysis of association of SNP markers as well as distinct MHC class I and II alleles with CHB, HLA-DRB1*04 and HLA-Cw*05 variants were significantly more frequently transmitted to affected individuals (p<0.03 and p<0.05, respectively), while HLA-DRB1*13 and HLA-Cw*06 variants were significantly less often transmitted to affected children (p<0.04 and p<0.03). We further observed marked association of increased paternal (but not maternal) HLA-DRB1*04 transmission to affected offspring (p<0.02).CONCLUSIONS: HLA-DRB1*04 and HLA-Cw*05 were identified as novel foetal HLA allele variants that confer susceptibility to CHB in response to Ro/SSA autoantibody exposure, while DRB1*13 and Cw*06 emerged as protective alleles. Additionally, we demonstrated a paternal contribution to foetal susceptibility to CHB for the first time.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Ostberg, Therese (author)
  • Salomonsson, StinaKarolinska Institutet (author)
  • Ding, Bo (author)
  • Eliasson, HåkanKarolinska Institutet (author)
  • Mälarstig, AndersKarolinska Institutet (author)
  • Alfredsson, LarsKarolinska Institutet (author)
  • Klareskog, LarsKarolinska Institutet (author)
  • Hamsten, AndersKarolinska Institutet (author)
  • Olsson, TomasKarolinska Institutet (author)
  • Axelsson, TomasUppsala universitet,Molekylär medicin(Swepub:uu)toaxe957 (author)
  • Gadler, FredrikKarolinska Institutet (author)
  • Jonzon, AndersUppsala universitet,Pediatrik(Swepub:uu)andersjz (author)
  • Sonesson, Sven-Erik (author)
  • Kockum, IngridKarolinska Institutet (author)
  • Wahren-Herlenius, MarieKarolinska Institutet (author)
  • Karolinska InstitutetMolekylär medicin (creator_code:org_t)

Related titles

  • In:Journal of Internal Medicine: Wiley275:6, s. 640-6510954-68201365-2796

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