DNA strands forming a pregnant woman, symbolizing the genetic link to recurrent pregnancy loss

Decoding Recurrent Pregnancy Loss: Are Your Genes the Key?

Mira Elwood in Health & Wellness November 2025 • 4 min read.

"Uncover the hidden genetic factors behind recurrent pregnancy loss and explore the potential of personalized thrombophilia panels."

Recurrent pregnancy loss (RPL), defined as two or more consecutive miscarriages before the 22nd week of gestation, affects approximately 5% of all pregnancies, impacting 1% of couples. While clinically silent fetal or maternal issues might be absent, placental vascular incidents often emerge as a primary suspect behind unexplained repeat abortions. It’s a challenging reality for many hoping to expand their families.

Genetic variations affecting blood coagulation genes can impair the encoded proteins, leading to thrombosis within placental vessels, placental detachment, and subsequent abortion. Methylenetetrahydrofolate reductase (MTHFR), factor V Leiden (FVL), factor II prothrombine, and factor VIII genes are well-known, forming a standard thrombophilia panel for RPL assessment in genetic labs worldwide. However, the complete picture remains elusive without considering other potential genetic contributors.

The roles of Human Platelet Antigen-1 (HPA-1) rs5918 T > C (C12548T) and fibrinogen-β (FGB) rs1800790 G > A polymorphisms in RPL, particularly among diverse populations, remains under investigation. Fibrinogen-β, a crucial coagulation pathway component, regulates endothelial activity and platelet aggregation. Variations in the FGB gene promoter might elevate fibrinogen levels, enhancing platelet-dependent coagulation—potentially triggering thromboembolic disorders and coronary artery diseases. Similarly, the C12548T variation in HPA-1, found on glycoprotein GPIIIa, influences platelet activation and thrombosis. Understanding these genetic links could pave the way for enhanced diagnostic and therapeutic strategies.

Unraveling the Genetic Connection: HPA-1, Fibrinogen, and RPL Risk

DNA strands forming a pregnant woman, symbolizing the genetic link to recurrent pregnancy loss

A recent study investigated the association between specific gene variants and recurrent pregnancy loss (RPL) in a group of women. Researchers focused on two key genes involved in blood clotting: HPA-1 (rs5918) and fibrinogen β chain (FGB rs1800790). These genes play critical roles in coagulation, and variations could potentially contribute to RPL. The study involved 110 women with a history of at least two consecutive spontaneous abortions and 110 healthy women as a control group. Researchers analyzed specific variations (rs5918 T > C and rs1800790 G > A) using PCR-RFLP techniques.

The study revealed that a specific variation in the HPA-1 gene (rs5918), specifically the heterozygote genotype (TC), was significantly associated with an increased risk of RPL. While the FGB gene variant (rs1800790) alone wasn't linked to RPL, its combination with the HPA-1 rs5918 polymorphism was associated with an elevated risk. This suggests a potential interplay between these genes in influencing RPL risk.

HPA-1 Gene (rs5918): The heterozygote genotype (TC) significantly increases RPL risk.
Fibrinogen β Chain (FGB rs1800790): While not individually linked, its combination with HPA-1 rs5918 elevates RPL risk.
Combined Impact: Cumulative effect of both polymorphisms significantly impacts RPL risk (p-value = 0.03).

These findings emphasize the critical roles of FGB and HPA-1 genes in coagulation and thrombosis. Including these polymorphisms in thrombophilia panels may enhance the detection rate of hereditary thrombophilia patients. However, further studies with larger sample sizes are essential to clarify the exact role of the studied gene polymorphisms, especially the FGB gene variant (rs1800790), in the pathogenesis of RPL. Understanding these genetic markers could refine risk assessment and personalized management in women experiencing RPL.

What's Next? Refining Diagnostic Approaches

The study underscores the potential benefits of incorporating HPA-1 and FGB gene variants into diagnostic thrombophilia panels for women experiencing RPL. This inclusion may lead to improved diagnosis and treatment strategies for thrombophilia-related disorders. Future research should focus on larger sample sizes and diverse populations to validate these findings and explore the complex interplay of genetic and environmental factors in RPL. Further understanding of these genetic components holds the promise of more effective interventions and improved outcomes for women facing recurrent pregnancy loss.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3390/medsci6040098, Alternate LINK

Title: Investigating Association Of Rs5918 Human Platelets Antigen 1 And Rs1800790 Fibrinogen Β Chain As Critical Players With Recurrent Pregnancy Loss

Subject: General Economics, Econometrics and Finance

Journal: Medical Sciences

Publisher: MDPI AG

Authors: Fatemeh Karami, Maliheh Askari, Mohammad Modarressi

Published: 2018-10-31

Everything You Need To Know

What is Recurrent Pregnancy Loss (RPL)?

Recurrent Pregnancy Loss (RPL) is defined as experiencing two or more consecutive miscarriages before the 22nd week of gestation. It affects approximately 5% of all pregnancies and impacts around 1% of couples. In many cases, the underlying causes may not be obvious, but placental vascular issues often emerge as a primary suspect. This condition presents a significant challenge for those hoping to expand their families, highlighting the importance of understanding the factors that contribute to RPL.

How do the HPA-1 and Fibrinogen genes relate to Recurrent Pregnancy Loss?

The Human Platelet Antigen-1 (HPA-1) and fibrinogen-β (FGB) genes are linked to Recurrent Pregnancy Loss (RPL due to their roles in blood coagulation. Variations in these genes, specifically the HPA-1 rs5918 T > C and FGB rs1800790 G > A polymorphisms, can affect platelet activation and coagulation pathways. A study showed that the heterozygote genotype (TC) of HPA-1 (rs5918) significantly increased the risk of RPL. Furthermore, the combination of FGB and HPA-1 polymorphisms was associated with an elevated risk. The understanding of these genetic links could enhance diagnostic and therapeutic strategies for RPL.

What is the significance of the HPA-1 rs5918 polymorphism in RPL?

The HPA-1 rs5918 polymorphism, specifically the heterozygote genotype (TC), is significantly associated with an increased risk of Recurrent Pregnancy Loss (RPL). This variation on glycoprotein GPIIIa influences platelet activation and thrombosis. The presence of this specific genetic variation suggests a higher likelihood of placental vascular incidents, which often are a primary cause of unexplained repeat abortions. This emphasizes the critical role of the HPA-1 gene in coagulation and the potential for this genetic marker to refine risk assessment and personalized management in women experiencing RPL.

What is the role of the Fibrinogen-β (FGB) gene in the context of RPL?

The fibrinogen-β (FGB) gene, particularly the rs1800790 G > A polymorphism, plays a role in RPL, although the study did not find a direct individual link to RPL. Fibrinogen-β is a crucial component of the coagulation pathway and regulates endothelial activity and platelet aggregation. Variations in the FGB gene promoter might elevate fibrinogen levels, potentially triggering thromboembolic disorders. While the study did not find an individual link to RPL, the combination of the FGB variant with the HPA-1 rs5918 polymorphism was associated with an elevated risk, highlighting the interplay between these genes. Understanding the combined impact of the FGB and HPA-1 genes can significantly impact RPL risk.

How can understanding HPA-1 and FGB genes improve the diagnosis and treatment of RPL?

Understanding the role of HPA-1 and FGB genes can improve the diagnosis and treatment of Recurrent Pregnancy Loss (RPL) by incorporating these gene variants into diagnostic thrombophilia panels. This inclusion may lead to improved diagnosis and treatment strategies for thrombophilia-related disorders. Specifically, recognizing the impact of the HPA-1 rs5918 and FGB rs1800790 polymorphisms can refine risk assessment and personalize management for women experiencing RPL. Including these polymorphisms in thrombophilia panels may enhance the detection rate of hereditary thrombophilia patients, potentially leading to earlier interventions and improved outcomes. Future research will focus on confirming these benefits with larger studies.