OBJECTIVE Haptoglobin is a haemoglobin-scavenging protein that binds and neutralises free haemoglobin and modulates inflammation and endothelial progenitor cell function. A HP gene copy number variation (CNV) generates HP1 and HP2 alleles, while the single-nucleotide polymorphism rs2000999 influences their levels. The HP1 allele is hypothesised to improve outcome after spontaneous (non-traumatic) intracerebral haemorrhage (ICH). We investigated the associations of the HP CNV genotype and rs2000999 with haematoma volume, perihaematomal oedema (PHO) volume, functional outcome and mortality after ICH. METHODS We included patients with neuroimaging-proven ICH, available DNA and 6-month follow-up in an observational cohort study (CROMIS-2). We classified patients into three groups according to the HP CNV: 1-1, 2-1 or 2-2 and also dichotomised HP into HP1-containing genotypes (HP1-1 and HP2-1) and HP2-2 to evaluate the HP1 allele. We measured ICH and PHO volume on CT; PHO was measured by oedema extension distance. Functional outcome was assessed by modified Rankin score (unfavourable outcome defined as mRS 3-6). RESULTS We included 731 patients (mean age 73.4, 43.5% female). Distribution of HP CNV genotype was: HP1-1 n=132 (18.1%); HP2-1 n=342 (46.8%); and HP2-2 n=257 (35.2%). In the multivariable model mortality comparisons between HP groups, HP2-2 as reference, were as follows: OR HP1-1 0.73, 95% CI 0.34 to 1.56 (p value=0.41) and OR HP2-1 0.5, 95% CI 0.28 to 0.89 (p value=0.02) (overall p value=0.06). We found no evidence of association of HP CNV or rs200999 with functional outcome, ICH volume or PHO volume. CONCLUSION The HP2-1 genotype might be associated with lower 6-month mortality after ICH; this finding merits further study.

中文翻译：

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自发性脑出血后的触珠蛋白基因型和结果。

目的 触珠蛋白是一种血红蛋白清除蛋白，可结合和中和游离血红蛋白，调节炎症和内皮祖细胞功能。HP 基因拷贝数变异 (CNV) 产生 HP1 和 HP2 等位基因，而单核苷酸多态性 rs2000999 影响它们的水平。假设 HP1 等位基因可改善自发性（非创伤性）脑出血 (ICH) 后的结果。我们研究了 HP CNV 基因型和 rs2000999 与 ICH 后血肿体积、血肿周围水肿 (PHO) 体积、功能结果和死亡率的关系。方法 我们在一项观察性队列研究 (CROMIS-2) 中纳入了经神经影像学证实的 ICH、可用 DNA 和 6 个月随访的患者。我们根据 HP CNV 将患者分为三组：1-1、2-1 或 2-2 以及将 HP 二分为含 HP1 的基因型（HP1-1 和 HP2-1）和 HP2-2 以评估 HP1 等位基因。我们在 CT 上测量了 ICH 和 PHO 体积；PHO通过水肿延伸距离测量。通过改良的 Rankin 评分（定义为 mRS 3-6 的不利结果）评估功能结果。结果 我们纳入了 731 名患者（平均年龄 73.4 岁，43.5% 为女性）。HP CNV基因型分布为：HP1-1 n=132 (18.1%)；HP2-1 n=342 (46.8%); 和 HP2-2 n = 257 (35.2%)。在 HP 组之间的多变量模型死亡率比较中，以 HP2-2 为参考值如下：OR HP1-1 0.73, 95% CI 0.34 至 1.56（p 值=0.41）和 OR HP2-1 0.5, 95% CI 0.28 至0.89（p 值=0.02）（总体 p 值=0.06）。我们没有发现 HP CNV 或 rs200999 与功能结果、ICH 体积或 PHO 体积相关的证据。结论 HP2-1 基因型可能与 ICH 后 6 个月死亡率降低有关；这一发现值得进一步研究。