Melanocortin-1 Receptor Polymorphisms and the Risk of Complicated Sepsis After Trauma: A Candidate Gene Association Study.
Melanocortin-1 Receptor Polymorphisms and the Risk of Complicated Sepsis After Trauma: A Candidate Gene Association Study.
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DOI：
10.1097/shk.0000000000000708
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发表时间：
2017-01
期刊：
影响因子：
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通讯作者：
Gibran NS
中科院分区：
文献类型：
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作者：
Seaton ME;Parent BA;Sood RF;Wurfel MM;Muffley LA;O'Keefe GE;Gibran NS
确定黑皮质素-1 受体 (MC1R) 单核苷酸多态性 (SNP) 是否与创伤后复杂脓毒症相关。医院感染是创伤后发病和死亡的重要原因。炎症相关基因中的几个 SNP 与脓毒症有关。 MC1R 是一种抗炎介质，可能参与创伤后的免疫反应。我们对之前报道的一项前瞻性队列研究中纳入的受试者的基因组 DNA 中的 8 个常见 MC1R SNP 进行了基因分型。受试者是入住一级创伤中心 ICU 的成年创伤患者（2003-2005 年）。分析中总共包括 1,246 名受试者。大多数是男性（70%）、严重受伤（81%）和钝器损伤（89%）。 40% 发展为脓毒症，23% 发展为复杂脓毒症，其定义为伴有器官功能障碍的脓毒症。在逻辑回归分析中，调整年龄、性别、体重指数、损伤严重程度评分、红细胞输注需求和损伤机制后，MC1RR163Q 变异 (rs885479) 与发生复杂败血症的较低风险相关 (ORadj=0.48, 95%CI: 0.28–0.81, p=0.006)。在具有全基因组 SNP 数据的 511 名受试者亚组中，在调整遗传亚结构（按主要成分）和上述临床因素后，MC1RR163Q 变异与复杂脓毒症之间的关联仍然显着（ORadj=0.30，95%CI：0.13-0.70，p=0.005）。 MC1RR163Q 与创伤后并发败血症的较低风险相关。 MC1R 的治疗目标可能对有复杂脓毒症风险的创伤患者有益。
To determine if melanocortin-1 receptor (MC1R) single nucleotide polymorphisms (SNPs) are associated with complicated sepsis after trauma. Nosocomial infections are an important cause of morbidity and mortality after trauma. Several SNPs in inflammation-related genes have been associated with sepsis. MC1R is an anti-inflammatory mediator that may be involved in the immune response after trauma. We genotyped 8 common MC1R SNPs in genomic DNA from subjects enrolled in a previously reported prospective cohort study. Subjects were adult trauma patients admitted to the ICU at a Level I trauma center (2003–2005). A total of 1,246 subjects were included in the analysis. The majority were male (70%), severely injured (81%), and injured by a blunt mechanism (89%). Forty percent developed sepsis, and 23% developed complicated sepsis, which was defined as sepsis with organ dysfunction. In logistic regression analysis, with adjustments for age, sex, body mass index, injury severity score, red blood cell transfusion requirement, and mechanism of injury, the MC1RR163Q variant (rs885479) was associated with a lower risk of developing complicated sepsis (ORadj=0.48, 95%CI: 0.28–0.81, p=0.006). In a subgroup of 511 subjects with genome-wide SNP data, the association between the MC1RR163Q variant and complicated sepsis remained significant after adjusting for genetic substructure (by principal components) and the above clinical factors (ORadj=0.30, 95%CI: 0.13–0.70, p=0.005). MC1RR163Q is associated with a lower risk of complicated sepsis after trauma. Therapeutic targeting of MC1R may be beneficial for trauma patients at risk for complicated sepsis.