Influence of TRPM4 rs8104571 genotype on intracranial pressure and outcomes in African Americans with traumatic brain injury
Abstract The TRPM4 gene codes for a membrane ion channel subunit related to inflammation in the central nervous system. Recent investigation has identified an association between TRPM4 single nucleotide polymorphisms (SNPs) rs8104571 and rs150391806 and increased intracranial (ICP) pressure followin...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-32819-7 |
| _version_ | 1797845974763175936 |
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| author | Joseph D. Krocker Madeline E. Cotton Jacob B. Schriner Baron K. Osborn Michael M. Talanker Yao-Wei W. Wang Charles S. Cox Charles E. Wade |
| author_facet | Joseph D. Krocker Madeline E. Cotton Jacob B. Schriner Baron K. Osborn Michael M. Talanker Yao-Wei W. Wang Charles S. Cox Charles E. Wade |
| author_sort | Joseph D. Krocker |
| collection | DOAJ |
| description | Abstract The TRPM4 gene codes for a membrane ion channel subunit related to inflammation in the central nervous system. Recent investigation has identified an association between TRPM4 single nucleotide polymorphisms (SNPs) rs8104571 and rs150391806 and increased intracranial (ICP) pressure following traumatic brain injury (TBI). We assessed the influence of these genotypes on clinical outcomes and ICP in TBI patients. We included 292 trauma patients with TBI. DNA extraction and real-time PCR were used for TRPM4 rs8104571 and rs150391806 allele discrimination. Five participants were determined to have the rs8104571 homozygous variant genotype, and 20 participants were identified as heterozygotes; 24 of these 25 participants were African American. No participants had rs150391806 variant alleles, preventing further analysis of this SNP. Genotypes containing the rs8104571 variant allele were associated with decreased Glasgow outcome scale-extended (GOSE) score (P = 0.0231), which was also consistent within our African-American subpopulation (P = 0.0324). Regression analysis identified an association between rs8104571 variant homozygotes and mortality within our overall population (P = 0.0230) and among African Americans (P = 0.0244). Participants with rs8104571 variant genotypes exhibited an overall increase in ICP (P = 0.0077), although a greater frequency of ICP measurements > 25 mmHg was observed in wild-type participants (P = < 0.0001). We report an association between the TRPM4 rs8104571 variant allele and poor outcomes following TBI. These findings can potentially be translated into a precision medicine approach for African Americans following TBI utilizing TRPM4-specific pharmaceutical interventions. Validation through larger cohorts is warranted. |
| first_indexed | 2024-04-09T17:47:38Z |
| format | Article |
| id | doaj.art-d350293ca1d4451a890a0d90031f6b45 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T17:47:38Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d350293ca1d4451a890a0d90031f6b452023-04-16T11:14:48ZengNature PortfolioScientific Reports2045-23222023-04-0113111110.1038/s41598-023-32819-7Influence of TRPM4 rs8104571 genotype on intracranial pressure and outcomes in African Americans with traumatic brain injuryJoseph D. Krocker0Madeline E. Cotton1Jacob B. Schriner2Baron K. Osborn3Michael M. Talanker4Yao-Wei W. Wang5Charles S. Cox6Charles E. Wade7Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at HoustonCenter for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at HoustonCenter for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at HoustonCenter for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at HoustonCenter for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at HoustonCenter for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at HoustonCenter for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at HoustonCenter for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at HoustonAbstract The TRPM4 gene codes for a membrane ion channel subunit related to inflammation in the central nervous system. Recent investigation has identified an association between TRPM4 single nucleotide polymorphisms (SNPs) rs8104571 and rs150391806 and increased intracranial (ICP) pressure following traumatic brain injury (TBI). We assessed the influence of these genotypes on clinical outcomes and ICP in TBI patients. We included 292 trauma patients with TBI. DNA extraction and real-time PCR were used for TRPM4 rs8104571 and rs150391806 allele discrimination. Five participants were determined to have the rs8104571 homozygous variant genotype, and 20 participants were identified as heterozygotes; 24 of these 25 participants were African American. No participants had rs150391806 variant alleles, preventing further analysis of this SNP. Genotypes containing the rs8104571 variant allele were associated with decreased Glasgow outcome scale-extended (GOSE) score (P = 0.0231), which was also consistent within our African-American subpopulation (P = 0.0324). Regression analysis identified an association between rs8104571 variant homozygotes and mortality within our overall population (P = 0.0230) and among African Americans (P = 0.0244). Participants with rs8104571 variant genotypes exhibited an overall increase in ICP (P = 0.0077), although a greater frequency of ICP measurements > 25 mmHg was observed in wild-type participants (P = < 0.0001). We report an association between the TRPM4 rs8104571 variant allele and poor outcomes following TBI. These findings can potentially be translated into a precision medicine approach for African Americans following TBI utilizing TRPM4-specific pharmaceutical interventions. Validation through larger cohorts is warranted.https://doi.org/10.1038/s41598-023-32819-7 |
| spellingShingle | Joseph D. Krocker Madeline E. Cotton Jacob B. Schriner Baron K. Osborn Michael M. Talanker Yao-Wei W. Wang Charles S. Cox Charles E. Wade Influence of TRPM4 rs8104571 genotype on intracranial pressure and outcomes in African Americans with traumatic brain injury Scientific Reports |
| title | Influence of TRPM4 rs8104571 genotype on intracranial pressure and outcomes in African Americans with traumatic brain injury |
| title_full | Influence of TRPM4 rs8104571 genotype on intracranial pressure and outcomes in African Americans with traumatic brain injury |
| title_fullStr | Influence of TRPM4 rs8104571 genotype on intracranial pressure and outcomes in African Americans with traumatic brain injury |
| title_full_unstemmed | Influence of TRPM4 rs8104571 genotype on intracranial pressure and outcomes in African Americans with traumatic brain injury |
| title_short | Influence of TRPM4 rs8104571 genotype on intracranial pressure and outcomes in African Americans with traumatic brain injury |
| title_sort | influence of trpm4 rs8104571 genotype on intracranial pressure and outcomes in african americans with traumatic brain injury |
| url | https://doi.org/10.1038/s41598-023-32819-7 |
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