Department of Gastroenterology, Gasthuisberg Hospital, KU Leuven, Belgium.
Gut. 2012 Apr;61(4):528-34. doi: 10.1136/gut.2011.240978. Epub 2011 Jun 27.
Haptoglobin (Hp) is a haemoglobin-binding protein with immunomodulatory properties. Its gene (16q22) harbours a common polymorphism with two different alleles: Hp1 and Hp2. Genotype Hp22 has been shown to be over-represented in different immune diseases. Results in Crohn's disease (CD) are contradictory.
To determine whether Hp plays a role in inflammatory bowel disease, both genetically and functionally.
1061 patients with CD, 755 with ulcerative colitis (UC) and 152 with primary sclerosing cholangitis, as well as 452 healthy controls, were genotyped using touch-down PCR. To confirm association results, 464 CD trios and 151 UC trios were genotyped. Serum Hp concentrations were determined in 62 individuals of different genotype. Colitis was induced in mice with dextran sulphate sodium (DSS) and oxazolone (Oxa). Cytokine production was evaluated by mRNA quantification in colonic tissue and ELISA on supernatants of mesenteric lymph node cells.
Prevalence of Hp2 was higher in CD and UC than in controls. In the confirmatory cohorts, Hp2 was over-transmitted to the affected offspring. Serum Hp concentrations were higher in individuals with genotypes Hp11 and Hp21 than in those with Hp22 (1.38 vs 0.89 g/l). DSS- and Oxa-induced colitis were more severe in Hp-deficient mice than in control mice and accompanied by higher concentrations (although not statistically significantly different) of tissue mRNA for cytokines. Interleukin-17 production was significantly higher in the presence of Hp-deficient serum compared with wild-type serum.
The Hp gene may play a role in susceptibility to inflammatory bowel disease. Its implication in other immune diseases underscores the common pathways between these diseases. Experimental models of colitis showed that Hp has a protective role in inflammatory colitis, most likely by inhibiting the production of Th1 and Th17 cytokines.
触珠蛋白（Hp）是一种具有免疫调节特性的血红蛋白结合蛋白。其基因（16q22）具有一个常见的多态性，有两个不同的等位基因：Hp1 和 Hp2。已经表明基因型 Hp22 在不同的免疫性疾病中过表达。在克罗恩病（CD）中的结果是矛盾的。
确定 Hp 是否在遗传和功能上都在炎症性肠病中起作用。
对 1061 例 CD 患者、755 例溃疡性结肠炎（UC）患者和 152 例原发性硬化性胆管炎患者以及 452 例健康对照者进行触珠蛋白基因分型，采用降落 PCR。为了确认关联结果，对 464 例 CD 三核苷酸和 151 例 UC 三核苷酸进行了基因分型。在不同基因型的 62 个人中测定血清 Hp 浓度。用葡聚糖硫酸钠（DSS）和氧化偶氮甲烷（Oxa）诱导小鼠结肠炎。通过对结肠组织的 mRNA 定量和肠系膜淋巴结细胞上清液的 ELISA 评估细胞因子的产生。
CD 和 UC 患者中 Hp2 的发生率高于对照组。在确认队列中，Hp2 向患病后代的传递过度。基因型 Hp11 和 Hp21 的个体血清 Hp 浓度高于 Hp22 个体（1.38 比 0.89 g/l）。与对照小鼠相比，Hp 缺陷小鼠的 DSS 和 Oxa 诱导的结肠炎更严重，尽管组织细胞因子的 mRNA 浓度（尽管无统计学意义）更高。与野生型血清相比，缺乏 Hp 的血清中白细胞介素-17 的产生明显更高。
Hp 基因可能在炎症性肠病的易感性中起作用。其在其他免疫性疾病中的意义突出了这些疾病之间的共同途径。结肠炎的实验模型表明，Hp 在炎症性结肠炎中具有保护作用，这很可能是通过抑制 Th1 和 Th17 细胞因子的产生。
