Zorzetto Michele, Bombieri Cristina, Ferrarotti Ilaria, Medaglia Sara, Agostini Carlo, Tinelli Carmine, Malerba Giovanni, Carrabino Natalia, Beretta Anna, Casali Lucio, Pozzi Ernesto, Pignatti Pier Franco, Semenzato Gianpietro, Cuccia Maria Clara, Luisetti Maurizio
Laboratorio di Biochimica e Genetica, Clinica di Malattie dell'Apparato Respiratorio, Pavia, Italy.
Am J Respir Cell Mol Biol. 2002 Jul;27(1):17-23. doi: 10.1165/ajrcmb.27.1.4805.
Sarcoidosis is likely to result from exposure of genetically susceptible hosts to environmental agents. Erythrocyte (E) complement receptor 1 (CR1) is a membrane protein mediating the transport of immune complexes (ICs) to phagocytes, and at least three polymorphisms on the CR1 gene are related to erythrocyte surface density of CR1 molecules, in turn related to the rate of IC clearance from circulation. We hypothesized that sarcoidosis could be associated with increased frequency of the CR1 gene alleles coding for reduced CR1/E ratio. We studied 91 sarcoid patients and two control groups: 94 healthy volunteers and 71 patients with chronic obstructive pulmonary disease (COPD). Three polymorphic sites of CR1 gene, His1208Arg, intron 27 HindIII/RFLP, and Pro1827Arg, were analyzed. The three polymorphisms were in linkage disequilibrium. The GG genotype for the Pro1827Arg (C(5507)G) polymorphism was significantly associated with sarcoidosis in comparison to both control groups (odds ratio [OR] = 3.13; 95% confidence interval [CI] 1.49-6.69 versus healthy control subjects, and OR= 2.82, 95% CI 1.27-6.39 versus COPD control subjects). The same genotype was particularly associated to disease in females (OR = 7.05; 95% CI 3.10-16.61 versus healthy control subjects). These findings agree with speculations on the role of CR1 gene as a possible susceptibility factor.
结节病可能是由于基因易感宿主暴露于环境因素所致。红细胞（E）补体受体1（CR1）是一种膜蛋白，介导免疫复合物（ICs）向吞噬细胞的转运，CR1基因上至少有三种多态性与CR1分子的红细胞表面密度相关，进而与循环中IC清除率相关。我们推测结节病可能与编码较低CR1/E比值的CR1基因等位基因频率增加有关。我们研究了91例结节病患者和两个对照组：94名健康志愿者和71例慢性阻塞性肺疾病（COPD）患者。分析了CR1基因的三个多态性位点，即His1208Arg、内含子27 HindIII/RFLP和Pro1827Arg。这三种多态性处于连锁不平衡状态。与两个对照组相比，Pro1827Arg（C(5507)G）多态性的GG基因型与结节病显著相关（优势比[OR]=3.13；95%置信区间[CI] 1.49 - 6.69，与健康对照受试者相比，以及OR = 2.82，95% CI 1.27 - 6.39，与COPD对照受试者相比）。相同的基因型在女性患者中与疾病的关联尤为明显（OR = 7.05；95% CI 3.10 - 16.61，与健康对照受试者相比）。这些发现与关于CR1基因作为可能的易感因素的作用的推测一致。
