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.