title: Possible Role of HLA-G, LILRB1 and KIR2DL4 Gene Polymorphisms in Spontaneous Miscarriage.
abstract: The KIR2DL4 receptor and its ligand HLA-G are considered important for fetal-maternal immune tolerance and successful pregnancy. The absence of a particular variant of KIR2DL4 might be a bad prognostic factor for pregnancy outcome. However, it could be compensated by the presence of the respective LILRB1 allele. Therefore, we investigated the KIR2DL4, LILRB1 and HLA-G polymorphisms in 277 couples with spontaneous abortion and 219 control couples by HRM, PCR-SSP and RFLP methods. We found a protective effect of women's heterozygosity in -716 HLA-G (p = 0.0206) and LILRB1 (p = 0.0131) against spontaneous abortion. Surprisingly, we observed more 9A/10A genotypes of KIR2DL4 gene carriers in the group of male partners from the miscarriage group in comparison to the men from the control group (p = 0.0288). Furthermore, there was no association of women's KIR2DL4 polymorphism with susceptibility to spontaneous abortion. Multivariate analysis indicated that women's -716 HLA-G and LILRB1 and men's KIR2DL4 9A/10A are important in terms of the protection or susceptibility to miscarriage, respectively (p = 0.00968). In conclusion, a woman's heterozygosity in HLA-G and LILRB1 might be an advantage for a success of reproduction, but the partner's heterozygosity in 9A/10A KIR2DL4 alleles might not.
authors.affiliation: Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wroclaw, Poland. izan@iitd.pan.wroc.pl.
authors.forename: Izabela
authors.initials: I
authors.lastname: Nowak
authors.affiliation: Department of Surgical, Endoscopic and Oncologic Gynecology, Polish Mothers' Memorial Hospital-Research Institute, Lodz, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Malinowski
authors.affiliation: First Chair and Clinic of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Barcz
authors.affiliation: Department of Gynecology and Gynecologic Oncology, Polish Mothers' Memorial Hospital-Research Institute, Lodz, Poland.
authors.forename: Jacek R
authors.initials: JR
authors.lastname: Wilczyński
authors.affiliation: Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wroclaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wroclaw, Poland.|Faculty of Physical Education and Physiotherapy, Opole University of Technology, Opole, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Majorczyk
authors.affiliation: Faculty of Physical Education and Physiotherapy, Opole University of Technology, Opole, Poland.|Obstetric Gynecological Department, Disctrict Hospital Strzelce Opolskie, Strzelce Opolskie, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Motak-Pochrzęst
authors.affiliation: APC, Medical Analyses, Lodz, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Banasik
authors.affiliation: Laboratory of Immunogenetics and Tissue Immunology, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wroclaw, Poland. pkusnier@iitd.pan.wroc.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuśnierczyk
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics / Q000276:immunology; D000022:Abortion, Spontaneous / Q000235:genetics* / Q000276:immunology*; D000328:Adult; D000368:Aged; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D059951:HLA-G Antigens / Q000235:genetics / Q000502:physiology*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007108:Immune Tolerance; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011256:Pregnancy Outcome; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D054345:Receptors, KIR2DL4 / Q000235:genetics / Q000502:physiology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D059951:HLA-G Antigens; C515079:KIR2DL4 protein, human; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic; D054345:Receptors, KIR2DL4
keywords: HLA-G; KIR2DL4; LILRB1; Linkage disequilibrium; Spontaneous abortion