KL-6 as a Biomarker for Adult Patients with Cystic Fibrosis and the Impact of MUC1 Genotype.

Background/Objectives: Krebs von den Lungen-6 (KL-6) is a mucin-like glycoprotein that is elevated in a variety of lung diseases and used as a diagnostic and prognostic biomarker in people with cystic fibrosis (pwCF). Single nucleotide polymorphisms (SNPs) in mucin-1 (MUC1) influence KL-6 serum concentration. This study investigated the relationship between serum KL-6 concentrations in pwCF and a MUC1 SNP and its longitudinal dynamics. Methods: The study included pwCF (n = 174) and healthy controls (n = 30). In pwCF, 365 samples were collected for longitudinal analyses; KL-6 levels were measured and the MUC1 SNP rs4072037 was genotyped in pwCF and controls. Cross-sectional and longitudinal associations between KL-6, genotype, and clinical parameters, such as infectious exacerbation, body mass index, inflammatory values and lung function, were analyzed using linear mixed-effects models. Results: Serum KL-6 was significantly elevated in pwCF compared with controls (458 ± 357 vs. 283 ± 103 U/mL; p < 0.001). Homozygous G/G carriers exhibited higher baseline KL-6 than A/A carriers (627 ± 673 vs. 397 ± 148 U/mL; p < 0.001), while heterozygous individuals showed intermediate levels. Longitudinally, the MUC1 SNP and interindividual differences in vital capacity (ppFVC) primarily determined baseline KL-6 levels, explaining 52.5% of variance. Short-term intraindividual fluctuations were largely driven by infectious exacerbations independent of genotype, accounting for ~10% of within-subject variance. Conclusions: PwCF generally showed elevated serum KL-6 levels and reflected both stable interindividual differences, mainly driven by the MUC1 SNP and ppFVC. Dynamic intraindividualchanges were associated with infectious exacerbations. Given the influence of MUC1 polymorphisms (e.g., rs4072037) on KL-6 concentration, personalized interpretation based on the genotype status may be informative in pwCF.