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

IF 2.1 4区 医学 Q3 IMMUNOLOGY Human Immunology Pub Date : 2025-03-01 Epub 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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白细胞介素17 RA和RC基因多态性与子痫前期风险增加:单一和联合遗传分析
背景子痫前期是一种以高血压和全身功能障碍为特征的主要妊娠并发症,严重影响孕产妇健康。该研究强调了妊娠期间触发的复杂免疫反应,特别是白细胞介素17信号通路在PE发病机制中的作用。本研究探讨了两个遗传变异il - 17ra rs4819554和IL-17RC rs708567与先兆子痫风险之间的关系。方法采用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)对470名确诊为PE的女性(其中240名确诊为PE的女性和230名对照组)进行了病例对照研究。此外,还进行了一项新的计算研究来预测这些多态性的可能作用。结果研究发现IL-17 RA rs4819554的AG、GG基因型和IL-17RC rs708567的TT基因型与子痫前期风险增加有显著相关性,尤其是重症。值得注意的是,结合这些多态性进一步增加了风险,IL-17 RA rs4819554 GG/ IL-17RC rs708567 CC基因型与晚发性PE风险增加6倍相关。这些发现强调了IL-17受体基因变异作为子痫前期易感性的生物标志物的潜力,并提示妊娠期间影响炎症的遗传因素之间存在复杂的相互作用。根据计算机研究,IL-17RA rs4819554基因多态性可能导致等位基因表达差异。此外,生物信息学研究表明,IL-17RC rs708567 SNP会导致其二级结构和理化特性发生显著变化。结论本研究为子痫前期的遗传机制提供了重要的见解,强调了进一步研究这些遗传变异及其对妊娠结局的影响的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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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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