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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00005-016-0389-7) contains supplementary material, which is available to authorized users.

The impact of HLA-G, LILRB1 and LILRB2 gene polymorphisms on susceptibility to and severity of endometriosis

“… Chr Chromosome; Genomic position is shown relative to GRCh38.p7; SNP IDs are according to dbSNP (rs, http://www.ncbi.nlm.nih.gov/SNP ); c.*65_*66insATTTGTTCATGCCT was earlier described as 14 bp ins/del in 3′UTR of the HLA-G gene (Wiśniewski et al 2010 , 2015 ); NM_006669.6:c.1807-7G>A was earlier described as 5651 G>A (rs41308748) (Wiśniewski et al 2015 ; Nowak et al 2016 ); NM_006669.6:c.425T>C was earlier described as 927 T>C (rs1061680) (Davidson et al 2010 ), and were relative to the translation start site …”

Association of Soluble HLA-G Plasma Level and HLA-G Genetic Polymorphism With Pregnancy Outcome of Patients Undergoing in vitro Fertilization Embryo Transfer

“…Genomic position is shown relative to GRCh38.p7; SNP IDs are according to dbSNP (rs, http://www.ncbi.nlm.nih.gov/SNP); c.*65_*66insATTTGTTCATGCCT was earlier described as 14-bp ins/del in 3 ′ UTR of the HLA-G gene and were relative to the translation start site (43)(44)(45). Chr, chromosome.…”

The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population

“…This group comprised 219 healthy couples with at least 2 healthy-born children and no history of miscarriage or endocrinological or immunological disorders. Details concerning this control group were described by Nowak et al [ 26 , 27 ]. In addition, we decided to include 100 couples with one healthy-born child from anonymous paternity testing to increase the group of fertile couples to 319 to make our study stronger and more reliable.…”

“…Genomic DNA was isolated from venous blood by using the Invisorb Spin Blood Midi Kit (Invitek, Berlin, Germany) according to the manufacturer’s instructions. Procedures of MTHFR 677 C>T and 1298 A>C genotyping have been published recently in detail in supplementary material of our article [ 27 ].…”