Department of Acute and Tertiary Care, School of Nursing;
J Neurosurg. 2014 Feb;120(2):386-90. doi: 10.3171/2013.10.JNS13219. Epub 2013 Nov 29.
Haptoglobin allele heterogeneity has been implicated in differential reactive oxidant inhibition and inflammation. Haptoglobin α2-α2 has a lower affinity for binding hemoglobin, and when bound to hemoglobin, is cleared less easily by the body. The authors hypothesized that haptoglobin α2-α2 genotype should be less protective for downstream injury after aneurysmal subarachnoid hemorrhage (aSAH) and should portend a worse outcome.
Patients with Fisher Grade 2 or higher aSAH were enrolled in the study. Genotyping for haptoglobin genotype was performed from blood and/or CSF. Demographic information, medical condition variables, and hospital course were abstracted from the medical record upon enrollment into the study. Outcome data (modified Rankin Scale score, Glasgow Outcome Scale score, and mortality) were collected at 3 months posthemorrhage.
The authors enrolled 193 patients who ranged in age from 18 to 75 years. Only Caucasians were used in this analysis to minimize bias from variable haptoglobin allele frequencies in populations of different ancestral backgrounds. The sample had more women than men (overall mean age 54.45 years). Haptoglobin α2 homozygotes were older than the other individuals in the study sample (57.27 vs 53.2 years, respectively; p = 0.02) and were more likely to have Fisher Grade 3 SAH (p = 0.02). Haptoglobin α2-α2 genotype, along with Fisher grade and Hunt and Hess grade, was associated with a worse 3-month outcome compared to those with the haptoglobin α1-α1 genotype according to modified Rankin Scale score after controlling for covariates (OR 4.138, p = 0.0463).
Patients with aSAH who carry the haptoglobin α2-α2 genotype had a worse outcome. Interestingly, the presence of a single α-2 allele was associated with worse outcome, suggesting that the haptoglobin α-2 protein may play a role in the pathology of brain injury following aSAH, although the mechanism for this finding requires further research. The haptoglobin genotype may provide additional information on individual risk of secondary injury and recovery to guide care focused on improving outcomes.
触珠蛋白等位基因异质性与活性氧化抑制和炎症的差异有关。触珠蛋白 α2-α2 与血红蛋白的结合亲和力较低，并且与血红蛋白结合后，身体更不容易清除。作者假设触珠蛋白 α2-α2 基因型对动脉瘤性蛛网膜下腔出血（aSAH）后下游损伤的保护作用应较低，并预示着预后较差。
本研究纳入了 Fisher 分级 2 级或更高的 aSAH 患者。从血液和/或 CSF 中进行触珠蛋白基因型检测。在入组研究时，从病历中提取人口统计学信息、医疗状况变量和住院情况。在出血后 3 个月收集预后数据（改良 Rankin 量表评分、格拉斯哥结局量表评分和死亡率）。
作者共纳入了 193 名年龄在 18 至 75 岁之间的患者。为了最大限度地减少不同祖裔背景人群中触珠蛋白等位基因频率变化带来的偏差，本分析仅使用了白种人。该样本中女性多于男性（总体平均年龄为 54.45 岁）。触珠蛋白 α2 纯合子比研究样本中的其他个体年龄更大（分别为 57.27 岁和 53.2 岁；p=0.02），且更有可能患有 Fisher 3 级 SAH（p=0.02）。在控制了协变量后，触珠蛋白 α2-α2 基因型与 Fisher 分级、Hunt 和 Hess 分级一起，与改良 Rankin 量表评分的 3 个月预后较差相关，而与触珠蛋白 α1-α1 基因型相比（OR 4.138，p=0.0463）。
携带触珠蛋白 α2-α2 基因型的 aSAH 患者预后较差。有趣的是，单个 α-2 等位基因的存在与预后较差相关，这表明触珠蛋白 α-2 蛋白可能在 aSAH 后脑损伤的病理机制中发挥作用，尽管这一发现的机制需要进一步研究。触珠蛋白基因型可能为个体继发性损伤和恢复的风险提供额外信息，以指导以改善预后为重点的护理。
