Elevated MBL concentrations are not an indication of association between the MBL2 gene and type 1 diabetes or diabetic nephropathy

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 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.

FIG. 1.

Box plot diagram showing the distribution of serum MBL concentrations, for patients with type 1 diabetes, stratified by nephropathy status. Black horizontal lines, median values; □, interquartile ranges; ○, outliers. The median serum concentration of MBL was higher in patients with macroalbuminuria (median 1,881 μg/l [interquartile range 608–3,124]) than in patients with normal AER (1,548 μg/l [514–2,635]), P = 0.019. The median concentration was 1,645 μg/l (531–3,220) in patients with microalbuminuria and 1,359 μg/l (343–2798) in patients with ESRD, P = 0.17 and P = 0.45, respectively, compared with patients with normal AER.

FIG. 2.

Distribution of serum MBL concentrations in patients with normal AER and patients with macroalbuminuria, stratified by the MBL2 diplotype.