Relationship Between TRPM4 RS8104571 Genotype, Circulating TRPM4 and SUR1, and Clinical Outcome Following Traumatic Brain Injury

Authors

Joseph D Krocker
Madeline E Cotton
Janet R Ashley
Jacob B Schriner
Baron K Osborn
Yao-Wei Willa Wang
Charles S Cox
Charles E Wade

Language

English

Publication Date

1-1-2025

Journal

Shock

DOI

10.1097/SHK.0000000000002468

PMID

39227352

PMCID

PMC11742263

PubMedCentral® Posted Date

1-1-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

The variant single nucleotide polymorphism rs8104571 has been associated with poor outcomes following traumatic brain injury (TBI) and is most prevalent in those of African ancestry. This single nucleotide polymorphism (SNP) resides within a gene coding for the TRPM4 protein, which complexes with SUR1 protein to create a transmembrane ion channel and is believed to contribute to cellular swelling and cell death in neurological tissue. Our study evaluates the relationship between circulating TRPM4 and SUR1, rs8104571 genotype, and clinical outcome in TBI patients. Trauma patients with moderate to severe TBI were included in this retrospective study. rs8104571 genotyping and admission plasma TRPM4 and SUR1 quantification were performed with real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Adequate plasma for TRPM4 and SUR1 ELISA quantification was available for 289 patients, 54 of whom were African American (AA). Plasma TRPM4 concentration was increased in those with a variant rs8104571 allele compared with wild type when controlling for demographics and injury characteristics in the overall cohort ( P = 0.04) and within the AA subgroup ( P = 0.01). There was no significant association between plasma TRPM4 or SUR1 and clinical outcome (each P > 0.05). Plasma TRPM4 abundance increased with acute kidney injury severity ( P = 0.02). The association between increased plasma TRPM4 and variant rs810457 supports an underlying mechanism involving increased neuroinflammation with a subsequent increase in the leakage of TRPM4 from the central nervous system into circulation. Alternative sources of plasma TRPM4 including the kidney cannot be excluded and may play a significant role in the pathophysiology of trauma as well.

Keywords

Humans, TRPM Cation Channels, Brain Injuries, Traumatic, Male, Female, Adult, Middle Aged, Polymorphism, Single Nucleotide, Genotype, Retrospective Studies, Sulfonylurea Receptors, Aged, Traumatic brain injury, personalized medicine, precision medicine, polymorphism, biomarker, TRPM4, SUR1, rs8104571

Published Open-Access

yes

Recommended Citation

Krocker, Joseph D; Cotton, Madeline E; Ashley, Janet R; et al., "Relationship Between TRPM4 RS8104571 Genotype, Circulating TRPM4 and SUR1, and Clinical Outcome Following Traumatic Brain Injury" (2025). Faculty, Staff and Student Publications. 5496.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5496