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Histidine-rich glycoprotein gene polymorphism in patients with recurrent miscarriage
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Reproduktiv hälsa/Sundström-Poromaa)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Obstetrisk forskning/Högberg)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Klinisk och experimentell reproduktionsbiologi)
Department of Clinical Sciences, Division of Obstetrics and Gynaecology, Karolinska Institute, Danderyd Hospital.
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2013 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 8, 974-977 p.Article in journal (Refereed) Published
Abstract [en]

Association between the histidine-rich glycoprotein (HRG) C633T single nucleotide polymorphism (SNP) and recurrent miscarriage was investigated in a case-control study. The cases constituted 187 women with recurrent miscarriage that were compared with 395 controls who had delivered a child and had no history of miscarriage. Blood samples were collected from each woman, genomic DNA was extracted and genotyped for the HRG C633T SNP. In the whole study population, the percentage of miscarriage was the same, regardless of genotype (C/C 31.2%, C/T 32.9% and T/T 32.5%). However, an association between homozygous T/T carriers and recurrent miscarriage was detected in a subgroup of women with primary recurrent miscarriage (odds ratio 2.44, 95% CI 1.01-5.92). Our results indicate an important role for the HRG C633T SNP in the occurrence of recurrent miscarriage.

Place, publisher, year, edition, pages
John Wiley & Sons, 2013. Vol. 92, no 8, 974-977 p.
Keyword [en]
Genotype, histidine-rich glycoprotein, infertility, recurrent miscarriage, single nucleotide polymorphism
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-207015DOI: 10.1111/aogs.12155ISI: 000321820100015OAI: oai:DiVA.org:uu-207015DiVA: diva2:647111
Available from: 2013-09-10 Created: 2013-09-09 Last updated: 2016-08-26
In thesis
1. The Histidine-rich Glycoprotein in Reproduction
Open this publication in new window or tab >>The Histidine-rich Glycoprotein in Reproduction
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Infertility affects 15% of reproductive-aged couples. The milieu surrounding the growing embryo is of outmost importance, and should be optimised during in vitro fertilisation (IVF). Many biological processes, such as angiogenesis, coagulation, and immune processes need to be well regulated for a pregnancy to occur and progress normally. Histidine-rich glycoprotein (HRG) is a plasma protein that regulates components of these systems by building complexes with various ligands. A single nucleotide polymorphism (SNP) in HRG, denoted HRG C633T, seem to be of importance for IVF treatment outcomes. The aim of this thesis was to further investigate the proposed human fertility effects of the HRG C633T SNP.

According to the findings of this thesis, the HRG C633T genotype is associated with primary recurrent miscarriage. Male HRG C633T genotype is associated with semen characteristics in infertile men, and pregnancy rates following IVF. However, the distribution of the HRG C633T SNP does not differ between infertile and fertile couples.

We further examined the role of the region surrounding the HRG C633T SNP for regulation of endometrial angiogenesis and human embryo development. The region affects primary endometrial endothelial cell migration, proliferation and tube-formation in vitro but does not appear to affect human embryo development. No effect of the HRG peptide was noted on the secretome of human embryos. However, early embryos secrete proteins into the surrounding culture media and the level of secretion of VEGF-A, IL-6, EMMPRIN and PlGF is greater in embryos of higher developmental stages.

In conclusion, the HRG C633T genotype appears to play a role only if infertility is established. The region surrounding HRG C633T SNP is of relevance in vitro for regulation of human endometrial endothelial cell angiogenesis. To predict which embryos to transfer in IVF, we have highlighted a number of proteins of interest for further investigation.     

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 76 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1244
Angiogenesis, embryo culture medium, embryogenesis, embryonic secretome, endometrium, histidine-rich glycoprotein, human embryo development, human embryo implantation, human endometrial endothelial cells, in vitro fertilisation, infertility, male infertility, proximity extension assay, recurrent miscarriage, single nucleotide polymorphism, sperm quality, time-lapse technique, vascular endothelial growth factor
National Category
Medical and Health Sciences Obstetrics, Gynecology and Reproductive Medicine Cell and Molecular Biology
urn:nbn:se:uu:diva-300769 (URN)978-91-554-9648-7 (ISBN)
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Public defence
2016-09-30, Auditorium minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:15 (English)
Available from: 2016-09-09 Created: 2016-08-12 Last updated: 2016-09-13

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Lindgren, Karin E.Kårehed, KarinKarypidis, HelenaStavreus-Evers, AnneliSundström Poromaa, IngerÅkerud, Helena
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Department of Women's and Children's Health
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Acta Obstetricia et Gynecologica Scandinavica
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