Gordon Anthony C, Waheed Umeer, Hansen Troels K, Hitman Graham A, Garrard Christopher S, Turner Malcolm W, Klein Nigel J, Brett Stephen J, Hinds Charles J
Institute of Cell and Molecular Science, William Harvey Research Institute, Barts, UK.
Shock. 2006 Jan;25(1):88-93. doi: 10.1097/01.shk.0000186928.57109.8d.
Mannose-binding lectin (MBL) genetic polymorphisms result in deficiency of the encoded protein and increased susceptibility to infection, especially in children and the immunocompromised. The objective of this study was to investigate the relationship between MBL-2 exon 1 and promoter -221 polymorphisms, plasma levels of the encoded protein, and the incidence and outcome of severe sepsis and septic shock. One hundred seventy-four white adult patients with severe sepsis or septic shock were recruited in a prospective multicenter study across eight intensive care units in the South of England, UK. Genotype and haplotype frequencies were compared between normal population controls and patients, and between survivors and nonsurvivors. Plasma levels of encoded protein were related to genotype and outcome. The exon 1 polymorphisms (A/O or O/O) were significantly more common in the patients with severe sepsis and septic shock than in normal healthy adults (54.6% vs. 39.7%, P = 0.001), and there was a significant difference in haplotype frequency between controls and septic patients (P < 0.0001). There was no significant difference in MBL-2 genotype or haplotype frequency between survivors and nonsurvivors. There was a strong relationship between MBL-2 haplotype and plasma MBL concentration (P < 0.001). Individual plasma levels were variable and increased between days 1 and 7. The mortality rate was higher in those with MBL levels <1000 microg/L than in those patients with levels >1000 microg/L (47.2 vs. 22.2%, P = 0.05). We conclude that genetic polymorphisms resulting in mannose-binding lectin deficiency are associated with increased susceptibility to sepsis. The close relationship between polymorphic variants and plasma MBL concentration persists during sepsis but individual levels vary widely. Lower circulating MBL levels are associated with a poor outcome.
甘露糖结合凝集素（MBL）基因多态性导致编码蛋白缺乏，并增加感染易感性，尤其是在儿童和免疫功能低下者中。本研究的目的是探讨MBL-2外显子1和启动子-221多态性、编码蛋白的血浆水平与严重脓毒症和脓毒性休克的发生率及转归之间的关系。在英国英格兰南部的8个重症监护病房进行的一项前瞻性多中心研究中，招募了174例患有严重脓毒症或脓毒性休克的成年白人患者。比较了正常人群对照组与患者之间以及存活者与非存活者之间的基因型和单倍型频率。编码蛋白的血浆水平与基因型及转归相关。严重脓毒症和脓毒性休克患者中外显子1多态性（A/O或O/O）显著比正常健康成年人更常见（54.6%对39.7%，P = 0.001），对照组与脓毒症患者之间的单倍型频率存在显著差异（P < 0.0001）。存活者与非存活者之间的MBL-2基因型或单倍型频率无显著差异。MBL-2单倍型与血浆MBL浓度之间存在密切关系（P < 0.001）。个体血浆水平存在差异，且在第1天至第7天之间升高。MBL水平<1000μg/L者的死亡率高于MBL水平>1000μg/L的患者（47.2%对22.2%，P = 0.05）。我们得出结论，导致甘露糖结合凝集素缺乏的基因多态性与脓毒症易感性增加有关。多态性变体与血浆MBL浓度之间的密切关系在脓毒症期间持续存在，但个体水平差异很大。循环MBL水平较低与不良转归相关。
