Papp Maria, Foldi Ildiko, Nemes Eva, Udvardy Miklos, Harsfalvi Jolan, Altorjay Istvan, Mate Istvan, Dinya Tamas, Varvolgyi Csaba, Barta Zsolt, Veres Gabor, Lakatos Peter Laszlo, Tumpek Judit, Toth Laszlo, Szathmari Erzsebet, Kapitany Aniko, Gyetvai Agnes, Korponay-Szabo Ilma R
Second Department of Medicine, University of Debrecen, Debrecen, Hungary.
Clin Chem. 2008 Apr;54(4):697-704. doi: 10.1373/clinchem.2007.098780. Epub 2008 Feb 7.
Haptoglobin (Hp) alpha-chain alleles 1 and 2 account for 3 phenotypes that may influence the course of inflammatory diseases via biologically important differences in their antioxidant, scavenging, and immunomodulatory properties. Hp1-1 genotype results in the production of small dimeric, Hp2-1 linear, and Hp2-2 cyclic polymeric haptoglobin molecules. We investigated the haptoglobin polymorphism in patients with celiac disease and its possible association to the presenting symptoms.
We studied 712 unrelated, biopsy-proven Hungarian celiac patients (357 children, 355 adults; severe malabsorption 32.9%, minor gastrointestinal symptoms 22.8%, iron deficiency anemia 9.4%, dermatitis herpetiformis 15.6%, silent disease 7.2%, other 12.1%) and 384 healthy subjects. We determined haptoglobin phenotypes by gel electrophoresis and assigned corresponding genotypes.
Hp2-1 was associated with a significant risk for celiac disease (P = 0.0006, odds ratio [OR] 1.54, 95% CI 1.20-1.98; prevalence 56.9% in patients vs 46.1% in controls). It was also overrepresented among patients with mild symptoms (69.2%) or silent disease (72.5%). Hp2-2 was less frequent in patients than in controls (P = 0.0023), but patients having this phenotype were at an increased risk for severe malabsorption (OR 2.21, 95% CI 1.60-3.07) and accounted for 45.3% of all malabsorption cases. Celiac and dermatitis herpetiformis patients showed similar haptoglobin phenotype distributions.
The haptoglobin polymorphism is associated with susceptibility to celiac disease and its clinical presentations. The predominant genotype in the celiac population was Hp2-1, but Hp2-2 predisposed to a more severe clinical course. The phenotype-dependent effect of haptoglobin may result from the molecule's structural and functional properties.
触珠蛋白（Hp）α链等位基因1和2产生3种表型，这些表型因其抗氧化、清除和免疫调节特性存在生物学重要差异，可能影响炎症性疾病的病程。Hp1-1基因型导致产生小的二聚体触珠蛋白分子、Hp2-1线性分子和Hp2-2环状多聚体触珠蛋白分子。我们研究了乳糜泻患者的触珠蛋白多态性及其与所表现症状的可能关联。
我们研究了712名经活检证实的无亲缘关系的匈牙利乳糜泻患者（357名儿童，355名成人；严重吸收不良32.9%，轻微胃肠道症状22.8%，缺铁性贫血9.4%，疱疹样皮炎15.6%，无症状疾病7.2%，其他12.1%）和384名健康受试者。我们通过凝胶电泳确定触珠蛋白表型并确定相应的基因型。
Hp2-1与患乳糜泻的显著风险相关（P = 0.0006，比值比[OR] 1.54，95%置信区间1.20 - 1.98；患者患病率56.9%，对照组患病率46.1%）。在症状轻微（69.2%）或无症状疾病（72.5%）的患者中也占比过高。Hp2-2在患者中的频率低于对照组（P = 0.0023），但具有这种表型的患者严重吸收不良风险增加（OR 2.21，95%置信区间1.60 - 3.07），占所有吸收不良病例的45.3%。乳糜泻患者和疱疹样皮炎患者表现出相似的触珠蛋白表型分布。
触珠蛋白多态性与乳糜泻易感性及其临床表现相关。乳糜泻人群中主要的基因型是Hp2-1，但Hp2-2易导致更严重的临床病程。触珠蛋白的表型依赖性效应可能源于该分子的结构和功能特性。
