Elevated MBL Concentrations Are Not an Indication of Association Between the MBL2 Gene and Type 1 Diabetes or Diabetic Nephropathy

doi:10.2337/db08-1495

Elevated MBL Concentrations Are Not an Indication of Association Between the MBL2 Gene and Type 1 Diabetes or Diabetic Nephropathy

¹Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland;
²Institute of Molecular Medicine in Finland, Genome and Technology Center, Helsinki, Finland;
³Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland;
⁴The Medical Research Laboratories, Clinical Institute, Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus, Denmark.

Corresponding author: Mari Kaunisto, mari.kaunisto{at}helsinki.fi.

Abstract

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.

RESEARCH DESIGN AND 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 × 10⁻⁸¹–7 × 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.

Footnotes

*A complete list of the FinnDiane Study Group can be found in the online appendix.
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- Received October 28, 2008.
- Accepted March 25, 2009.
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