DNA strand intertwined with the human body, surrounded by faint outline suggesting immune system.

Sepsis Susceptibility: Is it in Your Genes?

Elliot Brynn in Health & Wellness December 2025 • 4 min read.

"Decoding the HMGB1 Gene and Its Role in Sepsis Outcomes for Chinese Han Individuals."

Sepsis, a life-threatening condition arising from the body's overwhelming response to an infection, remains a major global health challenge. Characterized by a complex interplay of factors, sepsis can rapidly lead to organ damage and even death. While medical advancements have improved treatment strategies, sepsis continues to pose a significant threat, especially for vulnerable populations.

One key player in the development of sepsis is the High Mobility Group Box 1 (HMGB1) protein, a late inflammatory mediator. Recent research suggests that genetic variations in the HMGB1 gene may influence an individual's susceptibility to sepsis and the severity of its outcomes. Understanding these genetic links could pave the way for personalized approaches to sepsis prevention and treatment.

This article delves into a recent study investigating the association between specific HMGB1 gene polymorphisms (rs2249825, rs1045411, and rs1360485) and sepsis susceptibility in Chinese Han patients. We'll explore how these genetic variations might impact an individual's risk and clinical outcomes, offering valuable insights into the genetic landscape of sepsis.

Decoding the HMGB1 Gene: Genetic Clues to Sepsis Risk

DNA strand intertwined with the human body, surrounded by faint outline suggesting immune system.

A study published in Gene (2018) explored the connection between HMGB1 gene variations and sepsis in Chinese Han patients. The researchers analyzed the genetic makeup of 345 sepsis patients and 345 healthy controls, focusing on three specific single nucleotide polymorphisms (SNPs): rs2249825, rs1045411, and rs1360485. SNPs are variations in a single DNA building block, and they can influence how genes function.

The study revealed significant associations between certain HMGB1 gene SNPs and sepsis risk. Specifically, the rs2249825 and rs1045411 SNPs were linked to an increased susceptibility to sepsis. However, the rs1360485 SNP did not show a significant association with sepsis risk in this population.

rs2249825 and rs1045411: These SNPs were associated with higher serum HMGB1 levels, indicating a potential link between these genetic variations and increased inflammation in sepsis.
APACHE II Scores: Patients with mutations in the rs2249825 and rs1045411 sites had higher APACHE II scores, a measure of disease severity, suggesting a more severe sepsis presentation.
Survival Rates: Individuals with mutant genotypes at the rs2249825 and rs1045411 sites experienced lower 30-day survival rates, highlighting the potential impact of these genetic variations on sepsis outcomes.

Further analysis pinpointed specific alleles (versions of a gene) that may increase sepsis risk. The rs2249825 locus C allele and the rs1045411 locus A allele were identified as high-risk factors for sepsis and severity in the Chinese Han population. These findings suggest that individuals carrying these specific genetic markers may be more vulnerable to developing sepsis and experiencing adverse outcomes.

The Future of Sepsis: Personalized Approaches Through Genetics

This study provides valuable insights into the genetic factors that may influence sepsis susceptibility and outcomes in Chinese Han patients. By identifying specific HMGB1 gene polymorphisms associated with increased risk and severity, researchers are paving the way for personalized approaches to sepsis management.

Further research is needed to validate these findings in larger and more diverse populations. Understanding the precise mechanisms by which these genetic variations influence HMGB1 expression and inflammatory responses could lead to the development of targeted therapies to mitigate sepsis risk and improve patient outcomes.

Ultimately, incorporating genetic information into sepsis risk assessment and treatment strategies could revolutionize how we approach this deadly condition, moving towards a future of personalized medicine where interventions are tailored to an individual's unique genetic profile.

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: 10.1016/j.gene.2018.11.027, Alternate LINK

Title: Associations Between Hmgb1 Gene Polymorphisms And Susceptibility And Clinical Outcomes In Chinese Han Sepsis Patients

Subject: Genetics

Journal: Gene

Publisher: Elsevier BV

Authors: Pingfeng Qiu, Licheng Wang, Jianming Ni, Yunlong Zhang

Published: 2019-03-01

Everything You Need To Know

What is sepsis, and what role does the HMGB1 protein play in its development?

Sepsis arises from an overwhelming immune response to an infection, leading to potential organ damage and death. The High Mobility Group Box 1 (HMGB1) protein, a late inflammatory mediator, plays a significant role in its development. Genetic variations in the HMGB1 gene may influence an individual's susceptibility and the severity of sepsis outcomes.

Which specific genetic variations within the HMGB1 gene were examined in the study, and why were they chosen?

The study focused on three specific single nucleotide polymorphisms (SNPs) within the HMGB1 gene: rs2249825, rs1045411, and rs1360485. SNPs are variations in a single DNA building block that can affect gene function. The study aimed to determine if these SNPs were associated with sepsis risk in Chinese Han patients.

What were the key findings regarding the association between the identified HMGB1 gene SNPs and sepsis risk in the Chinese Han population?

The study revealed that the rs2249825 and rs1045411 SNPs in the HMGB1 gene were associated with an increased susceptibility to sepsis in the Chinese Han population. Individuals with mutations in these sites had higher serum HMGB1 levels, indicating a potential link between these genetic variations and increased inflammation. However, the rs1360485 SNP did not show a significant association with sepsis risk in this population.

How do APACHE II scores and survival rates relate to the HMGB1 gene polymorphisms identified in the study?

APACHE II scores are a measure of disease severity. The study showed that patients with mutations in the rs2249825 and rs1045411 sites of the HMGB1 gene had higher APACHE II scores, suggesting a more severe sepsis presentation. Furthermore, individuals with mutant genotypes at these sites experienced lower 30-day survival rates, indicating the impact of these genetic variations on sepsis outcomes.

How might identifying specific HMGB1 gene polymorphisms help in the future management and treatment of sepsis, and what are the potential implications for personalized medicine?

The identification of specific HMGB1 gene polymorphisms, such as the rs2249825 locus C allele and the rs1045411 locus A allele, as high-risk factors for sepsis and severity in the Chinese Han population paves the way for personalized approaches to sepsis management. By understanding an individual's genetic predisposition, healthcare providers can tailor prevention and treatment strategies to improve outcomes. This approach might involve targeted therapies or closer monitoring of individuals carrying these specific genetic markers. Further research is needed to translate these findings into clinical practice and to explore the potential benefits of genetic screening for sepsis risk assessment.