University of British Columbia, Critical Care Research Laboratories, Institute for Heart+Lung Health, St. Paul's Hospital, Vancouver, BC, Canada.
Respirology. 2012 Nov;17(8):1253-60. doi: 10.1111/j.1440-1843.2012.02244.x.
Interleukin-8 (IL-8) is a central chemokine in acute respiratory distress syndrome (ARDS), and the IL-8 gene contains a functional single nucleotide polymorphism (SNP) -251A/T in its promoter region. We hypothesized that IL-8 -251A/T SNP is associated with PaO(2)/FiO(2) in critically ill patients.
We conducted genetic-association studies in intensive care units at academic teaching centres using a derivation septic shock cohort (vasopressin and septic shock trial (VASST), n = 467) and a validation post-cardiopulmonary bypass surgery cohort (CPB, n = 739) of Caucasian patients. Patients in both cohorts were genotyped for IL-8 -251A/T. The primary outcome variable in both cohorts was the fraction of patients who had a PaO(2) /FiO(2) < 200. IL-8 mRNA expression was measured in genotyped lymphoblastoid cells in vitro.
The frequency of the patients with PaO(2)/FiO(2) <200 was significantly greater in patients who had the AA genotype of -251A/T than in patients who had the AT or TT genotypes in both VASST (AA = 60.8% vs AT and TT = 53.8% and 48.0%, P = 0.038) and the CPB cohort (AA = 37.0% vs AT and TT = 27.0% and 26.0%, P = 0.039). Patients having the AA genotype had a higher probability to remain on mechanical ventilation (P = 0.047) in the first 14 days. Lymphoblastoid cells having the AA genotype had significantly higher IL-8 mRNA expression than cells having the AT or TT genotype (P = 0.022).
Critically ill Caucasian patients who had the AA genotype of IL-8 -251A/T had an increased risk of PaO(2)/FiO(2) <200. The AA genotype was associated with greater IL-8 mRNA expression than the AT or TT genotypes.
白细胞介素-8（IL-8）是急性呼吸窘迫综合征（ARDS）中的一种重要趋化因子，其基因启动子区域存在一个功能性单核苷酸多态性（SNP）-251A/T。我们假设 IL-8-251A/T SNP 与危重病患者的 PaO2/FiO2 有关。
我们在学术教学中心的重症监护病房进行了遗传关联研究，使用了一个衍生的感染性休克队列（血管加压素和感染性休克试验（VASST），n=467）和一个验证性体外循环手术后队列（CPB，n=739）的白种人患者。两个队列的患者均进行了 IL-8-251A/T 基因分型。两个队列的主要结局变量均为 PaO2/FiO2<200 的患者比例。体外对基因分型的淋巴母细胞系进行了 IL-8 mRNA 表达的测量。
VASST（AA=60.8% vs AT 和 TT=53.8% 和 48.0%，P=0.038）和 CPB 队列（AA=37.0% vs AT 和 TT=27.0% 和 26.0%，P=0.039）中，AA 基因型患者的 PaO2/FiO2<200 的频率明显高于 AT 和 TT 基因型患者。AA 基因型患者在机械通气的前 14 天内更有可能需要通气（P=0.047）。AA 基因型的淋巴母细胞系的 IL-8 mRNA 表达明显高于 AT 或 TT 基因型的细胞（P=0.022）。
危重病白种人患者的 IL-8-251A/T 为 AA 基因型时，PaO2/FiO2<200 的风险增加。AA 基因型与 AT 或 TT 基因型相比，IL-8 mRNA 表达更高。
