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SMIM1 variants rs1175550 and rs143702418 independently modulate Vel blood group antigen expression

Christophersen, Mikael K. LU ; Jöud, Magnus LU ; Ajore, Ram LU ; Vege, Sunitha; WICKELGREN LJUNGDAHL, KLARA LU ; Westhoff, Connie M; Olsson, Martin L. LU ; Storry, Jill R. LU and Nilsson, Björn LU (2017) In Scientific Reports 7.
Abstract

The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located in SMIM1 intron 2 in Swedish blood donors, and observed a strong correlation between expression and rs1175550 as well as with a previously unreported tri-nucleotide insertion (rs143702418; C > CGCA). While the two variants are tightly linked in Caucasians, we separated their effects in African Americans, and found that rs1175550G and to a... (More)

The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located in SMIM1 intron 2 in Swedish blood donors, and observed a strong correlation between expression and rs1175550 as well as with a previously unreported tri-nucleotide insertion (rs143702418; C > CGCA). While the two variants are tightly linked in Caucasians, we separated their effects in African Americans, and found that rs1175550G and to a lesser extent rs143702418C independently increase SMIM1 and Vel antigen expression. Gel shift and luciferase assays indicate that both variants are transcriptionally active, and we identified binding of the transcription factor TAL1 as a potential mediator of the increased expression associated with rs1175550G. Our results provide insight into the regulatory logic of Vel antigen expression, and extend the set of markers for genetic Vel blood group typing.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
7
publisher
Nature Publishing Group
external identifiers
  • scopus:85009518349
  • wos:000391927600001
ISSN
2045-2322
DOI
10.1038/srep40451
language
English
LU publication?
yes
id
87a03bc9-14d0-41e0-a552-b52b3fc573a8
date added to LUP
2017-02-28 12:09:43
date last changed
2018-01-07 11:53:10
@article{87a03bc9-14d0-41e0-a552-b52b3fc573a8,
  abstract     = {<p>The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located in SMIM1 intron 2 in Swedish blood donors, and observed a strong correlation between expression and rs1175550 as well as with a previously unreported tri-nucleotide insertion (rs143702418; C &gt; CGCA). While the two variants are tightly linked in Caucasians, we separated their effects in African Americans, and found that rs1175550G and to a lesser extent rs143702418C independently increase SMIM1 and Vel antigen expression. Gel shift and luciferase assays indicate that both variants are transcriptionally active, and we identified binding of the transcription factor TAL1 as a potential mediator of the increased expression associated with rs1175550G. Our results provide insight into the regulatory logic of Vel antigen expression, and extend the set of markers for genetic Vel blood group typing.</p>},
  articleno    = {40451},
  author       = {Christophersen, Mikael K. and Jöud, Magnus and Ajore, Ram and Vege, Sunitha and WICKELGREN LJUNGDAHL, KLARA and Westhoff, Connie M and Olsson, Martin L. and Storry, Jill R. and Nilsson, Björn},
  issn         = {2045-2322},
  language     = {eng},
  month        = {01},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {SMIM1 variants rs1175550 and rs143702418 independently modulate Vel blood group antigen expression},
  url          = {http://dx.doi.org/10.1038/srep40451},
  volume       = {7},
  year         = {2017},
}