Interleukin 17 RA and RC gene polymorphisms and increased preeclampsia risk: Single and combined genetic analysis
Mohammad Amin Norouzi1, Danial Jahantigh1, Forough Forghani2
1Department of Biology Faculty of Science University of Sistan and Baluchestan Zahedan Iran.
Insights
Genetic variants in IL-17RA and IL-17RC are linked to increased preeclampsia risk. Specific genotypes, particularly combined polymorphisms, significantly elevate the likelihood of developing this pregnancy complication.
Area of Science:
- Genetics
- Immunology
- Obstetrics
Background:
- Preeclampsia (PE) is a serious pregnancy complication marked by hypertension and systemic dysfunction.
- Immune responses during pregnancy, especially the interleukin 17 (IL-17) signaling pathway, are implicated in PE pathogenesis.
- This study investigates the association between IL-17RA rs4819554 and IL-17RC rs708567 genetic variants and preeclampsia risk.
Purpose of the Study:
- To examine the association between specific genetic variants in IL-17RA and IL-17RC and the risk of developing preeclampsia.
- To explore the potential of these genetic polymorphisms as biomarkers for preeclampsia susceptibility.
Main Methods:
- A case-control study involving 470 women (240 with PE, 230 controls).
- Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
- In-silico and bioinformatics analyses were conducted to predict the functional impact of the identified polymorphisms.
Main Results:
- Significant correlations were found between IL-17RA rs4819554 (AG, GG genotypes) and IL-17RC rs708567 (TT genotype) with increased preeclampsia risk.
- Combined polymorphisms, specifically IL-17RA rs4819554 GG/IL-17RC rs708567 CC, showed a six-fold increase in late-onset PE risk.
- In-silico studies suggested differential allelic expression for IL-17RA rs4819554 and structural/physicochemical changes for IL-17RC rs708567.
Conclusions:
- The study identifies specific IL-17 receptor gene variants as potential biomarkers for preeclampsia susceptibility.
- Findings suggest a complex interplay of genetic factors influencing pregnancy inflammation and PE development.
- Further research is warranted to elucidate the genetic mechanisms and implications for pregnancy outcomes.
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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