Genetic influences on Mannan-binding lectin (MBL) and Mannan-binding lectin associated serine protease-2 (MASP-2) activity

The lectin pathway of the complement system is activated when Mannan-binding lectin (MBL) in complex with MASP-2 binds microorganisms. Polymorphisms in both genes are responsible for low serum levels, which associate with increased risk of infection and autoimmune disease. The present study includes 1215 MBL measurements and 1214 MASP-2 activity measurements in healthy Danish adult twins. Total MASP-2 activity was estimated by C4 cleaving activity of samples diluted in an excess of MBL. Twin-twin correlations were higher in monozygotic (MZ) than in dizygotic (DZ) twins for both traits. Heritabilites of MBL levels and MASP-2 activity were estimated using structural equation modeling allowing assessment of the contribution of common genes affecting both traits. The estimated heritability was 0.77 [95% CI 0.64;0.91] for MBL levels and 0.75 [95% CI 0.59;0.81] for MASP-2 activity with the presence of additive genetic factors, shared environmental factors, and non-shared environmental factors. The genetic correlation, i.e., common genetic factors affecting MBL and MASP-2 activity was estimated to r(g) = 0.34 [0.25;0.42]. The data indicate a strong genetic influence for the serum levels of MBL and for MASP-2 activity with a significant genetic correlation between the two traits.