Prevalence of Toxoplasma gondii During Pregnancy and the Function of the IL6-174 G>C Mutation

Toxoplasma gondii is an intracellular parasite that leads to congenital toxoplasmosis and to neuro-ocular sequelae in newborns, some of which are severe, stillbirth and miscarriage. Polymorphisms in cytokine genes is one factor of the host genome that might be involved in the susceptibility to infection during prenatal period. In this study, the susceptibility of pregnant women to Toxoplasma gondii infection was investigated in relation to IL6 174 G>C (rs1800795) polymorphism.

Methods: The Women's and Children's Hospital in Babylon, Iraq, undertook a case control study from November 2024 to February 2024. Fifty pregnant women were included in the study; 20 of them were cases with proven T. gondii infection (anti IgG positive) and 30 were healthy controls who tested negative for the parasite. Allele Specific PCR for the IL6 174 G>C polymorphism was used for genotyping. A computerised VIDAS Toxo IgG II (ELFA) developed by bioMérieux in France was used to screen the sera for anti-T. gondii IgG antibodies. Logistic regression was used for estimation of odds ratio (OR) under the codominant, dominant and recessive genetic model, and Fisher's exact test was used to compare the frequencies of geno/alleles.

Results: In the cases, the GC heterozygote was significantly more common (50%) than in the controls (16.7%). There was a significant in the overall genotype distribution between the two groups (Fisher's exact test; P = 0.041). Under the codominant model, with GG as the reference, logistic regression analysis showed association of the GC genotype with an increased risk of infection (OR = 5.667, 95% CI: 1.369–23.462, P = 0.017). The model with overdominant high risk for heterozygotes (GC vs. GG+CC) was confirmed with strong and statistically significant increased risk (OR = 5.000, 95% CI: 1.363–18.348, P = 0.015). There was no significant found between the CC homozygote (OR = 1.417, P = 0.653). The control group was not in Hardy Weinberg equilibrium (χ² = 12.05, df = 1, P < 0.001), which was due to the small sample size.

Conclusion: The IL6 174 G>C polymorphism and specially the heterozygote GC is more susceptible to the Toxoplasma gondii during pregnancy. This could be due to an over-dominant effect, in which one copy of the C allele changes the regulation of interleukin 6, which could upset the Th1/Th2 balance that is necessary for parasite control and foetal immune tolerance. Prior to clinical translation, bigger multicenter prospective trials with direct measurement of blood IL 6 levels are necessary to assess the polymorphism's potential as a genetic marker for risk stratification in prenatal treatment.