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MBL and MASP-2 concentrations in serum and MBL2 promoter polymorphisms are associated to schizophrenia

  • Leslie Foldager (a1) (a2), Rudi Steffensen (a3), Steffen Thiel (a4), Thomas Damm Als (a1) (a5), Hans Jørgen Nielsen (a6), Merete Nordentoft (a7), Preben Bo Mortensen (a8), Ole Mors (a1) and Jens Christian Jensenius (a4)...

Extract

Objective: Causative relations between infections and psychosis, especially schizophrenia, have been speculated for more than a century, suggesting a hypothesis of association between schizophrenia and hereditary immune defects. Mannan-binding lectin (MBL) is a pattern-recognition molecule of the innate immune defence. MBL deficiency is the most common hereditary defect in the immune system and may predispose to infection and autoimmunity. Mannan-binding lectin serine protease-2 (MASP-2) is an MBL-associated serine protease mediating complement activation upon binding of MBL/MASP to microorganisms. The objective was to investigate if schizophrenia is associated with serum concentrations of MBL and MASP-2 or with genetic variants of the genes MBL2 and MASP2 encoding these proteins.

Methods: The sample consisted of 100 patients with schizophrenia and 350 controls. Concentrations of MBL and MASP-2 in serum were measured and seven single nucleotide polymorphisms known to influence these concentrations were genotyped.

Results: Significant association of disease with genetic markers was found in MBL2 but not in MASP2. Significant difference in MBL serum concentration was found between patients and controls when adjusting for MBL2 haplotypes. For concentrations of MASP-2, a significant interaction effect between a MASP2 variant and disease was found. Interestingly, MASP-2 levels also depended significantly on variants in MBL2 exon 1.

Conclusion: This study supports previous studies showing increased complement activity in patients with schizophrenia, indicates aetiological heterogeneity among patients and underlines that multilocus genotypes have to be considered when investigating effects on MBL level. It appears that inclusion of additional components from the system of complement activation is warranted.

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Corresponding author

Leslie Foldager, Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Skovagervej 2, DK8240 Risskov, Denmark. Tel: +45 7847 1119; Fax: +45 7847 1108; E-mail: Leslie.Foldager@ps.rm.dk

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The following Supporting information is available for this article:

Appendix S1. Methods.

Table S1. Estimated median MBL concentration in serum.

Table S2. Estimated median MASP-2 concentration in serum.

Additional Supporting information may be found in the online version of this article.

Please note: Wiley-Blackwell Publishing is not responsible for the content or functionality of any supplementary materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.

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