RELATIONSHIP BETWEEN TRPM4 RS8104571 GENOTYPE, CIRCULATING TRPM4 AND SUR1, AND CLINICAL OUTCOME FOLLOWING TRAUMATIC BRAIN INJURY.

Autor:	Krocker JD; Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA., Cotton ME; Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA., Ashley JR; Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA., Schriner JB; Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA., Osborn BK; Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA., Wang YW; Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA., Cox CS Jr, Wade CE
Jazyk:	angličtina
Zdroj:	Shock (Augusta, Ga.) [Shock] 2024 Aug 28. Date of Electronic Publication: 2024 Aug 28.
DOI:	10.1097/SHK.0000000000002468
Abstrakt:	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 was 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 to 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. Competing Interests: Funding and Conflicts of Interest: This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health (T32GM008792). Additional funding was provided by the William Stamps Farish Fund, the Howell Family Foundation, and the James H. "Red" Duke Professorship. Dr. Cox reports additional support from the National Institutes of Health; Department of Defense-Medical Technology Enterprise Consortium; State of Texas Emerging Technology Fund; Generate Life Sciences, Inc.; Athersys, Inc.; Celgene Cellular Therapeutics; Cellvation, Inc.; Cellularity, Inc.; Hope Biosciences, Inc.; The Bentsen Foundation; Mission Connect; Let's Cure CP; Ladybug Foundation; Evelyn Griffin Foundation; Glassell Family Foundation; The George and Cynthia Mitchell Foundation; Grace R. Walls Endowment; Brown Foundation; Cellvation, Inc.; Coagulex, Inc.; EMIT Corporation. No other authors report funding or conflicts of interest. (Copyright © 2024 by the Shock Society.)
Databáze:	MEDLINE
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