Yonsei Med J.  2016 Jan;57(1):111-117. 10.3349/ymj.2016.57.1.111.

Associations between Single Nucleotide Polymorphisms of High Mobility Group Box 1 Protein and Clinical Outcomes in Korean Sepsis Patients

• Lee K
• Chang Y
• Song K
• Park YY
• Huh JW
• Hong SB
• Lim CM
• Koh Y

• KMID: 2466359
• DOI: http://doi.org/10.3349/ymj.2016.57.1.111

Abstract

PURPOSE
High mobility group box 1 (HMGB1) plays a central role in the pathogenesis of sepsis and multiple organ dysfunction syndromes. We investigated the associations of a single nucleotide polymorphism (SNP; rs1045411) in HMGB1 with various clinical parameters, severity, and prognosis in patients with sepsis, severe sepsis, or septic shock.
MATERIALS AND METHODS
We enrolled 212 adult patients followed for 28 days. All patients were genotyped for rs1045411, and the serum levels of HMGB1 and several cytokines were measured.
RESULTS
The proportions of patients according to genotype were GG (71.2%), GA (26.4%), and AA (2.4%). Among patients with chronic lung disease comorbidity, patients with a variant A allele had higher positive blood culture rates and higher levels of various cytokines [interleukin (IL)-1beta, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha] than those with the GG genotype. In the analysis of those with diabetes as a comorbidity, patients with a variant A allele had higher blood culture and Gram-negative culture rates than those with GG genotypes; these patients also had a higher levels of IL-17. In the analysis of those with sepsis caused by a respiratory tract infection, patients with a variant A allele had higher levels of IL-10 and IL-17 (all p<0.05). This polymorphism had no significant impact on patient survival.
CONCLUSION
The variant A allele of rs1045411 appears to be associated with a more severe inflammatory response than the GG genotype under specific conditions.

Keyword

High mobility group box 1; single nucleotide polymorphisms; rs1045411; sepsis; the variant A allele

MeSH Terms

Adult
Aged
Alleles
Asian Continental Ancestry Group/genetics
China/epidemiology
Cytokines/*blood/*genetics
Female
Genotype
HMGB1 Protein/blood/*genetics
Humans
Interleukin-10/genetics
Interleukin-17/genetics
Interleukin-6/blood
Male
Middle Aged
Polymorphism, Genetic/*genetics
Polymorphism, Single Nucleotide/*genetics
Prognosis
Republic of Korea
Sepsis/immunology/*metabolism/mortality
Shock, Septic/immunology/*metabolism/mortality
Survival
Tumor Necrosis Factor-alpha/genetics
Cytokines
HMGB1 Protein
Interleukin-10
Interleukin-17
Interleukin-6
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Genetic map of the three single nucleotide polymorphism (SNP) of the HMGB1. The three long vertical arrows indicate the locations of the three SNPs. E1 to E5 show the locations of the exons. The black boxes are the protein-coding regions, and boxes including oblique lines are untranslated regions (UTR). rs2249825, rs3742305, and rs1045411 are located in the 5'-UTR, intron 4, and the 3'-UTR, respectively.

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