Genetic alterations within TLR genes in development of Toxoplasma gondii infection among Polish pregnant women

Adv Med Sci. 2017 Sep;62(2):216-222. doi: 10.1016/j.advms.2017.02.002. Epub 2017 May 10.

Abstract

Purpose: The research was conducted to evaluate the role of genotypes, haplotypes and multiple-SNP variants in the range of TLR2, TLR4 and TLR9 single nucleotide polymorphisms (SNPs) in the development of Toxoplasma gondii infection among Polish pregnant women.

Material and methods: The study was performed for 116 Polish pregnant women, including 51 patients infected with T. gondii, and 65 age-matched control pregnant individuals. Genotypes in TLR2 2258 G>A, TLR4 896 A>G, TLR4 1196 C>T and TLR9 2848 G>A SNPs were estimated by self-designed, nested PCR-RFLP assays. Randomly selected PCR products, representative for distinct genotypes in the studied polymorphisms, were confirmed by sequencing. All the genotypes were calculated for Hardy-Weinberg (H-W) equilibrium and TLR4 variants were tested for linkage disequilibrium. Relationships were assessed between alleles, genotypes, haplotypes or multiple-SNP variants in TLR polymorphisms and the occurrence of T. gondii infection in pregnant women, using a logistic regression model.

Results: All the analyzed genotypes preserved the H-W equilibrium among the studied groups of patients (P>0.050). Similar distribution of distinct alleles and individual genotypes in TLR SNPs, as well as of haplotypes in TLR4 polymorphisms, were observed in T. gondii infected and control uninfected pregnant women. However, the GACG multiple-SNP variant, within the range of all the four studied polymorphisms, was correlated with a decreased risk of the parasitic infection (OR 0.52, 95% CI 0.28-0.97; P≤0.050).

Conclusions: The polymorphisms, located within TLR2, TLR4 and TLR9 genes, may be involved together in occurrence of T. gondii infection among Polish pregnant women.

Keywords: Genetic susceptibility; Pregnant women; Single nucleotide polymorphism (SNP); Toll-like receptor (TLR); Toxoplasma gondii.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / metabolism*
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Pregnancy Complications, Infectious / etiology*
  • Pregnancy Complications, Infectious / pathology
  • Prognosis
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 4 / genetics*
  • Toll-Like Receptor 9 / genetics*
  • Toxoplasma / isolation & purification
  • Toxoplasmosis / etiology*
  • Toxoplasmosis / pathology
  • Young Adult

Substances

  • Biomarkers
  • TLR2 protein, human
  • TLR4 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptor 9