Introduction: MASP-1 is the first protein in the activation of the lectin pathway and MASP-1 is, like its isoforms MASP-3 and MAp44, encoded by the MASP1 gene. Our aim was to explore associations between polymorphisms in MASP1 and corresponding concentrations of MASP-1, MASP-3, and MAp44 in plasma as well as the genetic contribution to the equilibrium between the three proteins.
Methods: Fifteen SNPs were genotyped in the MASP1 gene in 350 blood donors. Corresponding plasma concentrations of MASP-1, MASP-3, and MAp44 were measured.
Results: A total of 10 different SNPs showed associations with the concentration of one or some of the three proteins (rs113938200, rs190590338, rs35089177, rs3774275, rs67143992, rs698090, rs72549154, rs72549254, rs75284004, rs7625133), and several of these were in strong linkage. SNPs located in the mutually exclusive splice region had opposite effects on the protein concentrations. Being e.g. homozygote for the minor allele of rs3774275 was associated with an increase in median concentration of 13% in MASP-1(P=0.03), 29% in MAp44 (P<0.001), and a decrease in MASP-3 of 26% (P<0.001) compared to homozygosis for the major allele. Heterozygosis of rs113938200 (p.Asn368Asp in MAp44) was associated with a reduced MAp44 concentration of 61% (P=0.005). Rs190590338 located in the promoter region was associated in the heterozygote form with an increased MASP-1 concentration of 35% (P = 0.002). A multivariate linear regression model including sex, age, M- and H-ficolin, MBL, and the 15 SNPs explained 20-48% of the variation in the concentration of the three proteins and the SNPs investigated contributed with the most explanatory power (12-23%).
Discussion: The present study described 10 SNPs, which were associated with the concentration of one or some of the three proteins originating from the MASP1 gene and in a multivariate model it was shown that the SNPs contributed with the most explanatory power to the protein concentrations.