NRF2 Gene Polymorphisms, Preconception BMI and Their Interplay in Preeclampsia.
Ziye Li1, Suyan Guo1, Xuan Zhou1
1Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, China.
International Journal of Molecular Sciences
|July 15, 2026
Summary
Prepregnancy overweight/obesity increases preeclampsia risk, while underweight status reduces it. Specific nuclear factor erythroid 2-related factor-2 (NRF2) gene variations and their interactions with BMI also influence preeclampsia susceptibility.
Area of Science:
- Obstetrics and Gynecology
- Genetics
- Epidemiology
Background:
- Preeclampsia (PE) is a significant pregnancy complication.
- The roles of prepregnancy body mass index (BMI) and nuclear factor erythroid 2-related factor-2 (NRF2) gene polymorphisms in PE risk are not fully understood.
- Investigating the interplay between BMI, NRF2 genetics, and PE is crucial for risk assessment.
Purpose of the Study:
- To examine the associations between NRF2 gene polymorphisms, prepregnancy BMI, and their interactions with preeclampsia risk.
- To identify specific NRF2 single-nucleotide polymorphisms (SNPs) and BMI categories associated with altered PE susceptibility.
Main Methods:
- A case-control study involving 198 PE patients and 396 controls.
- Genotyping of nine NRF2 SNPs using the MassArray platform.
- Logistic regression analyses to assess associations and interactions between prepregnancy BMI, NRF2 polymorphisms, and PE risk.
Main Results:
- Prepregnancy overweight/obesity (BMI ≥ 24.0 kg/m² ) significantly elevated PE risk (aOR=4.59), while underweight (BMI < 18.5 kg/m²) reduced it (aOR=0.38).
- NRF2 polymorphism rs13005431 showed a protective effect (aOR=0.59).
- Significant interactions were found between overweight/obesity and NRF2 polymorphisms rs35652124 (aOR=0.24) and rs2627765 (aOR=3.62) in relation to PE risk.
Conclusions:
- Prepregnancy BMI and NRF2 gene polymorphisms are independent risk factors for preeclampsia.
- Interactions between BMI status and specific NRF2 polymorphisms significantly modulate PE susceptibility.
- Combined assessment of metabolic and genetic factors may improve preeclampsia risk prediction.
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