Center for Translational Injury Research, Department of Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, 6431 Fannin St., MSB 5.204, Houston, TX, 77030, USA.
Department of Pediatric Surgery, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA.
Sci Rep. 2023 Apr 10;13(1):5815. doi: 10.1038/s41598-023-32819-7.
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.
TRPM4 基因编码一种与中枢神经系统炎症有关的膜离子通道亚基。最近的研究发现，TRPM4 单核苷酸多态性（SNP）rs8104571 和 rs150391806 与创伤性脑损伤（TBI）后颅内压（ICP）升高有关。我们评估了这些基因型对 TBI 患者的临床结果和 ICP 的影响。我们纳入了 292 名创伤性 TBI 患者。使用 DNA 提取和实时 PCR 对 TRPM4 rs8104571 和 rs150391806 等位基因进行区分。有 5 名参与者被确定为 rs8104571 纯合变异基因型，20 名参与者为杂合子；其中 24 名参与者为非裔美国人。没有参与者携带 rs150391806 变异等位基因，因此无法进一步分析该 SNP。含有 rs8104571 变异等位基因的基因型与格拉斯哥预后评分扩展（GOSE）评分降低相关（P=0.0231），在我们的非裔美国人亚群中也是如此（P=0.0324）。回归分析发现，在我们的总体人群中，rs8104571 变异纯合子与死亡率之间存在关联（P=0.0230），在非裔美国人中也是如此（P=0.0244）。携带 rs8104571 变异基因型的参与者的 ICP 总体升高（P=0.0077），尽管野生型参与者的 ICP 测量值>25mmHg 的频率更高（P<0.0001）。我们报告了 TRPM4 rs8104571 变异等位基因与 TBI 后不良结局之间的关联。这些发现可能会转化为一种针对 TBI 后非裔美国人的精准医疗方法，利用 TRPM4 特异性药物干预。需要通过更大的队列进行验证。
