Genetic Predisposition to Unexplained Recurrent Pregnancy Loss: Killer Cell Immunoglobulin-Like Receptor Gene Polymorphisms as Potential Biomarkers

Genet Test Mol Biomarkers. 2019 Jan;23(1):57-65. doi: 10.1089/gtmb.2018.0082. Epub 2018 Dec 26.

Abstract

Aim: The aim of this study was to investigate the association between killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and unexplained recurrent pregnancy loss (URPL).

Materials and methods: This study included 70 URPL patients with a history of two or more miscarriages and 70 healthy multiparous women as a control group. KIR genotyping was performed in all subjects for the KIRs 2DL1-4 and 2DS1-5 genes using polymerase chain reaction with sequence-specific primers.

Results: There was a significant relationship between the KIR genotypes and URPL. We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype was not detected in either the case or control group. Gene-gene interactions for all genes were statistically significant. The KIR Bx genotype was found primarily in the case group, and at a higher frequency when compared with the control group. There was a significant relationship between the URPL cases and Bx haplotypes.

Conclusion: We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype of the KIR gene, however, was not detected in either the case or control group. The observations reported herein on KIR genotyping offer a new avenue for innovations in biomarker research concerning URPL and other complex obstetrics diseases.

Keywords: KIRs; genotype; polymorphisms; pregnancy loss; uterine natural killer cells.

MeSH terms

  • Abortion, Habitual / genetics*
  • Adult
  • Alleles
  • Biomarkers
  • Case-Control Studies
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Haplotypes
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • Pregnancy
  • Receptors, KIR / genetics*
  • Turkey

Substances

  • Biomarkers
  • Receptors, KIR