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.
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
S S
0000-0002-4443-0446
SS
Krogh
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
C B
CB
Holt
Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
R
R
Steffensen
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
K L
KL
Funck
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
P
P
Høyem
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
E
E
Laugesen
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
P L
PL
Poulsen
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
S
S
Thiel
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
T K
TK
Hansen
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 / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000032:analysis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013311:Streptozocin
D001786:Blood Glucose; D037601:Mannose-Binding Lectin; D013311:Streptozocin; C084067:MASP1 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases
complement; mannan-binding lectin-associated serine proteases; single nucleotide polymorphism; type 2 diabetes mellitus