Plasma levels of MASP-1, MASP-3 and MAp44 in patients with type 2 diabetes: influence of glycaemic control, body composition and polymorphisms in the MASP1 gene.
Mounting evidence indicates that adverse activation of the complement system plays a role in the development of diabetic vascular complications. Plasma levels of the complement proteins mannan-binding lectin (MBL) and its associated serine proteases (MASP-1 and MASP-2) are elevated in diabetes. We hypothesized that single nucleotide polymorphisms (SNPs) in the MASP1 gene may contribute to altered plasma levels of the belonging gene products; MASP-1, MASP-3 and mannan-binding lectin-associated protein of 44 kDa (MAp44) in patients with type 2 diabetes. To investigate this, we compared plasma levels of MASP-1, MASP-3 and MAp44 in 100 patients with type 2 diabetes and 100 sex- and age-matched controls. Ten carefully selected SNPs were analysed using TaqMan® genotyping assay. Additionally, we included a streptozotocin-induced diabetes mouse model to directly examine the effect of inducing diabetes on MASP-1 levels. MASP-1 levels were significantly higher among patients with type 2 diabetes compared with healthy controls (P = 0·017). Five SNPs (rs874603, rs72549254, rs3774275, rs67143992, rs850312) in the MASP1 gene were associated with plasma levels of MASP-1, MASP-3 and MAp44. In the diabetes mouse model, diabetic mice had significantly higher MASP-1 levels than control mice (P = 0·003). In conclusion, MASP-1 levels were higher among patients with type 2 diabetes and diabetic mice. The mechanism behind this increase remains elusive.
['Krogh|S S|SS|0000-0002-4443-0446', 'Holt|C B|CB|', 'Steffensen|R|R|', 'Funck|K L|KL|', 'Høyem|P|P|', 'Laugesen|E|E|', 'Poulsen|P L|PL|', 'Thiel|S|S|', 'Hansen|T K|TK|']
D000368:Aged D000818:Animals D001786:Blood Glucose D001823:Body Composition D016022:Case-Control Studies D003718:Denmark D003921:Diabetes Mellitus, Experimental D003924:Diabetes Mellitus, Type 2 D005260:Female D005838:Genotype D006801:Humans D016014:Linear Models D008297:Male D037601:Mannose-Binding Lectin D050606:Mannose-Binding Protein-Associated Serine Proteases D051379:Mice D008810:Mice, Inbred C57BL D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D013311:Streptozocin
complement single nucleotide polymorphism mannan-binding lectin-associated serine proteases type 2 diabetes mellitus