Janssen Rob, Kruit Adrian, Grutters Jan C, Ruven Henk J, Gerritsen Wim B, van den Bosch Jules M
Department of Pulmonology, St Antonius Hospital, Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands.
Am J Respir Cell Mol Biol. 2006 Apr;34(4):496-9. doi: 10.1165/rcmb.2005-0151OC. Epub 2005 Dec 15.
Krebs von den Lungen (KL)-6 offers a new perspective as a disease marker in pulmonary diseases. The aim of this study was to analyze whether serum KL-6 levels are dependent on the functional adenosine to guanine mucin-1 (MUC1) gene polymorphism at nucleotide position 568 in a well-characterized white population. Polymorphisms were determined in 327 healthy, white individuals and 74 patients with sarcoidosis, using a PCR-sequence-specific primer assay. The serum KL-6 levels were measured by ELISA. Significant differences between serum KL-6 levels of healthy subjects who were grouped according to MUC1 568 genotype were observed (P<0.0001) (mean+/-SEM): AA (195.2+/-9.9 U/ml; 95% confidence interval [CI], 175.7-214.8), AG (246.0+/-8.6 U/ml; 95% CI, 229.0-263.1), and GG (302.6+/-11.8 U/ml; 95%CI, 279.3-326.0). In the patients with sarcoidosis, the results were (mean+/-SD): AA (550.1+/-411.7; 95% CI, 380.2-720.1), AG (716.3+/-452.4; 95% CI, 547.4-885.2), GG (1,151.0+/-1122; 95% CI, 610.1-1692.0); P=0.02. Comparison of the KL-6 levels in which the 568 genotype was ignored rendered 6 out of 74 (7.5%) misclassifications of "elevated" versus "normal" KL-6 levels or vice versa. In conclusion, the MUC1 568 A to G polymorphism may be of interest for diagnostic purposes because our study delivered in vivo evidence that it contributes to interindividual variations in KL-6 levels.
克雷布斯肺（KL）-6作为肺部疾病的一种疾病标志物提供了一个新的视角。本研究的目的是分析在一个特征明确的白种人群中，血清KL-6水平是否依赖于核苷酸位置568处功能性腺苷到鸟嘌呤粘蛋白-1（MUC1）基因多态性。使用PCR序列特异性引物分析法在327名健康白种人和74名结节病患者中确定多态性。通过ELISA测定血清KL-6水平。观察到根据MUC1 568基因型分组的健康受试者血清KL-6水平之间存在显著差异（P<0.0001）（均值±标准误）：AA（195.2±9.9 U/ml；95%置信区间[CI]，175.7 - 214.8），AG（246.0±8.6 U/ml；95% CI，229.0 - 263.1），以及GG（302.6±11.8 U/ml；95% CI，279.3 - 326.0）。在结节病患者中，结果为（均值±标准差）：AA（550.1±411.7；95% CI，380.2 - 720.1），AG（716.3±452.4；95% CI，547.4 - 88,5.2），GG（1,151.0±1122；95% CI，610.1 - 1692.0）；P = 0.02。忽略568基因型时KL-6水平的比较导致74例中有６例（7.5%）“升高”与“正常”KL-6水平的错误分类，反之亦然。总之，MUC1 568 A到G多态性可能在诊断方面具有意义，因为我们的研究提供了体内证据表明它导致KL-6水平的个体间差异。
