Interleukin 17 RA and RC gene polymorphisms and increased preeclampsia risk: Single and combined genetic analysis

IF 3.1 4区 医学 Q3 IMMUNOLOGY Human Immunology Pub Date : 2025-02-04 DOI:10.1016/j.humimm.2025.111250
Mohammad Amin Norouzi , Danial Jahantigh , Forough Forghani , Mahnaz Rezaei , Saeedeh Ghazaey Zidanloo
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Abstract

Background

Preeclampsia is a major pregnancy complication characterized by hypertension and systemic dysfunction, significantly impacting maternal health. The study highlights the complex immune responses triggered during pregnancy, particularly focusing on the interleukin 17 signaling pathway in PE pathogenesis. This study examines the association between two genetic variants—IL-17RA rs4819554 and IL-17RC rs708567—and the risk of preeclampsia.

Methods

In this case-control study, a cohort of 470 women including 240 diagnosed with PE and 230 control women were examined utilizing polymerase chain reaction-restriction fragment length polymorphism techniques (PCR-RFLP). Additionally, a new computational study was conducted to prediction the possible roles of these polymorphisms.

Results

The research found significant correlations between the AG and GG genotypes of IL-17 RA rs4819554 and the TT genotype of IL-17RC rs708567 with increased preeclampsia risk, particularly severe cases. Notably, combining these polymorphisms further elevated the risk, with the IL-17 RA rs4819554 GG/ IL-17RC rs708567 CC genotype associated with a six-fold increase in late-onset PE risk. These findings underscore the potential of IL-17 receptor gene variants as biomarkers for preeclampsia susceptibility and suggest a complex interplay of genetic factors influencing inflammation during pregnancy. The IL-17RA rs4819554 gene polymorphism may result in differential allelic expression, according to in-silico study. Additionally, bioinformatics study revealed that the IL-17RC rs708567 SNP will result in a notable change to its secondary structure and physicochemical characteristics.

Conclusions

This study provides significant insights into the genetic mechanisms underlying preeclampsia, highlighting the necessity for further investigation into these genetic variants and their implications for pregnancy outcomes.
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来源期刊
Human Immunology
Human Immunology 医学-免疫学
CiteScore
5.40
自引率
7.40%
发文量
107
审稿时长
12 days
期刊介绍: The journal''s scope includes understanding the genetic and functional mechanisms that distinguish human individuals in their immune responses to allografts, pregnancy, infections or vaccines as well as the immune responses that lead to autoimmunity, allergy or drug hypersensitivity. It also includes examining the distribution of the genes controlling these responses in populations. Research areas include: Studies of the genetics, genomics, polymorphism, evolution, and population distribution of immune-related genes Studies of the expression, structure and function of the products of immune-related genes Immunogenetics of susceptibility to infectious and autoimmune disease, and allergy The role of the immune-related genes in hematopoietic stem cell, solid organ, and vascularized composite allograft transplant Histocompatibility studies including alloantibodies, epitope definition, and T cell alloreactivity Studies of immunologic tolerance and pregnancy T cell, B cell, NK and regulatory cell functions, particularly related to subjects within the journal''s scope Pharmacogenomics and vaccine development in the context of immune-related genes Human Immunology considers immune-related genes to include those encoding classical and non-classical HLA, KIR, MIC, minor histocompatibility antigens (mHAg), immunoglobulins, TCR, BCR, proteins involved in antigen processing and presentation, complement, Fc receptors, chemokines and cytokines. Other immune-related genes may be considered. Human Immunology is also interested in bioinformatics of immune-related genes and organizational topics impacting laboratory processes, organ allocation, clinical strategies, and registries related to autoimmunity and transplantation.
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