Elevated MBL concentrations are not an indication of association between the MBL2 gene and type 1 diabetes or diabetic nephropathy.
OBJECTIVE
Mannose-binding lectin (MBL) is an essential component of the acute-phase immune response and may thus play a role in the pathogenesis of type 1 diabetes and diabetic nephropathy. The serum concentration of MBL is mainly genetically determined, and elevated concentrations have been associated with both type 1 diabetes and diabetic nephropathy. Previous genetic studies have not been conclusive due to the small number of patients and polymorphisms studied. We investigated whether MBL2 polymorphisms are associated with type 1 diabetes or diabetic nephropathy and whether patients with nephropathy have elevated MBL concentrations as indicated previously. Furthermore, we studied the association between MBL2 polymorphisms and MBL concentration.


METHODS
We genotyped 20 MBL2 single nucleotide polymorphisms (SNPs) in a large, well-characterized Finnish case-control sample consisting of 1,297 patients with type 1 diabetes with or without nephropathy and 701 nondiabetic individuals. The serum concentration of MBL was available for 1,064 patients.


RESULTS
We found that 19 SNPs were associated with the MBL concentration (P = 3 x 10(-81)-7 x 10(-4)). MBL concentrations were higher in patients with macroalbuminuria compared with patients without nephropathy even when the patients were stratified by the MBL2 genotypic background in accordance with previous studies. However, no evidence of association between any of the SNPs or their haplotype combinations and type 1 diabetes or diabetic nephropathy was observed.


CONCLUSIONS
Although most of the MBL2 SNPs studied were associated with the MBL concentration, no common variations (neither single SNPs nor their haplotype combinations) confer risk of type 1 diabetes or diabetic nephropathy.
Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland. mari.kaunisto@helsinki.fi
Mari A
MA
Kaunisto
Lisa
L
Sjölind
Riitta
R
Sallinen
Kim
K
Pettersson-Fernholm
Markku
M
Saraheimo
Sara
S
Fröjdö
Carol
C
Forsblom
Johan
J
Fagerudd
Troels K
TK
Hansen
Allan
A
Flyvbjerg
Maija
M
Wessman
Per-Henrik
PH
Groop
D000328:Adult; D017668:Age of Onset; D000419:Albuminuria / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005387:Finland; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D044465:White People / Q000235:genetics
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases