Immunogenetic Interplay of IL-6 and IL-6R Genes Variants and Circulating IL-6 Levels in ‎Toxoplasma gondii-infected Women with Recurrent Pregnancy Loss.

Abstract

Background: Recurrent pregnancy loss (RPL) is a global health challenge in women. It has been reported that Toxoplasma gondii (T. gondii) infection and interleukin-6 (IL-6) bioavailability contribute to RPL.

Objective: This study investigated IL-6 and IL-6 receptor (IL-6R) gene polymorphisms and blood IL-6 levels in T. gondii-infected women with RPL.

Methods: The study comprised 163 women, including 83 infected (Group A: subgroups A1, A2) and 80 healthy (Group B). Demographic data, blood, and placental tissue samples were collected. The blood samples were screened for IL-6 levels through ELISA. DNA was extracted, and T. gondii-DNA was identified using PCR. IL-6 and IL-6R genes were amplified by PCR and sequenced using the Sanger method.

Results: The IL-6 gene -174G/C (p=0.005) and -597G/A (p=0.0012) polymorphisms were significantly associated, while the -572G/C polymorphism was insignificantly associated (p=0.143) with infection and RPL. The mean blood IL-6 level was significantly variable across all groups (p < 0.001). The IL-6 gene -174GG and -597GG genotypes, and the IL-6R gene AA genotype, were common in Group-A2 (47.5%, 37.5%, 50%) and Group-B (56.2%, 60%, 68.8%), respectively, and were also significantly associated with elevated blood IL-6 levels. The -572GG genotype was common and was not significantly associated with elevated blood IL-6 levels across all groups (p=0.143). The IL-6 gene -174CC and -597AA genotypes and IL-6R gene CC genotype were highly prevalent in Group-A1 (48.8%, 41.9%, and 51.1%, respectively) and associated with low blood IL-6 levels.

Conclusion: The IL-6 gene -174G/C, -597G/A, and IL-6R gene A/C polymorphisms play significant roles in RPL in women infected with T. gondii, and change IL-6 bioavailability.