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Background  KL-6, a human MUC1 mucin, is a sensitive biomarker for interstitial lung diseases including pulmonary alveolar proteinosis (PAP). A correlation between MUC1 gene single nucleotide polymorphism (SNP) rs4072037 genotype and serum KL-6 levels has been reported. This study was aimed at investigating the correlation between MUC1 SNP genotype, severity of disease and disease outcome in PAP.    Methods  Twenty four patients with PAP and 30 healthy volunteers were studied. MUC1 rs4072037 was detected by using a real-time polymerase chain reaction (RT-PCR). Genotyping was performed by pyrosequencing. KL-6 levels were measured in serum by Nanopia KL-6 assay (SEKISUI Diagnostics).    Results  The frequency of MUC1 rs4072037 alleles was significantly different between PAP patients and healthy volunteers (PAP, A/A 46 %, A/G 54 %, G/G 0 %; healthy controls, A/A 30 %, A/G 40 %, G/G 30 %;  p  = 0.013). Serum KL-6 levels were significantly higher in PAP patients than in controls ( p  &lt; 0.0001), and significantly higher in PAP patients with A/A genotype than in those with A/G genotype ( p  = 0.007). Patients with A/A genotype had higher alveolar-arterial oxygen difference (A-aDO 2 ) and lower DLco compared to those with A/G genotype ( p  = 0.027 and  p  = 0.012, respectively). Multivariate analysis, Kaplan-Meier analysis and C statistics showed that the rs4072037 A/A genotype was associated with higher rate of disease progression (HR: 5.557,  p  = 0.014).    Conclusions  MUC1 rs4072037 A/A genotype is associated with more severe pulmonary dysfunction and a higher rate of disease progression in PAP patients.

MUC1 gene polymorphisms are associated with serum KL-6 levels and pulmonary dysfunction in pulmonary alveolar proteinosis