Human Molecular Genetics Advance Access published online on September 14, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm265
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Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients
1 Department of Anaesthesiology and Intensive Care, Herlev, Copenhagen University Hospital, Denmark 2 Clinical Institute, Århus University, Denmark 3 Department of Clinical Immunology sect.7631, Denmark 4 Intensive Care Unit 4131, Rigshospitalet, Copenhagen University Hospital, Denmark 5 Department of Clinical Microbiology, Herlev, Copenhagen University Hospital, Denmark 6 Copenhagen Trial Unit, Rigshospitalet, Copenhagen University Hospital, Denmark
* Correspondence to: Dr. Peter Garred, Department of Clinical Immunology, sect: 7631, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen O, Denmark, Telephone: +45 35457631, FAX : +45 35398766, e-mail: garred{at}post5.tele.dk
Received June 22, 2007; Revised August 25, 2007; Accepted August 25, 2007
Polymorphisms in the MBL2 gene, which affect the structure and influence on the serum concentration of mannose-binding lectin (MBL), are associated with inflammatory and infectious conditions. The importance of MBL2 polymorphisms on outcome in critical ill patients is unclear. 532 consecutive critically ill patients admitted to an intensive care unit (ICU) were included over a period of 18 months. 533 individuals served as controls. Vital status was obtained 15.5 months after the last patient was included. MBL2 polymorphisms were determined by a PCR-based assay. Homozygosity for MBL2 variant alleles (O/O) causing MBL structural defects was associated with the highest adjusted mortality rate followed by homozygosity for the normal MBL2 allele (A/A) encoding high MBL levels, while heterozygous A/O patients had the most favourable outcome (P=0.015). MBL2 alleles were not associated with death in ICU (n= 166, P=0.7), but the association appeared soon after discharge from ICU (n=366): hazard ratio (HR) for O/O using A/A as reference was 1.33 (95%CI: 0.8-2.2) and for A/O it was 0.62 (95%CI: 0.4-0.8) respectively (P=0.0045) at completion. No difference in MBL2 frequency was observed between patients and controls at baseline, and between patients classified as having sepsis or not. However, patients with the MBL2 O/O genotype had an increased frequency of Gram-positive bacterial infection (P=0.01). Heterozygosity for MBL2 alleles confers a protective effect while homozygosity is associated with the worst outcome soon after discharge from ICU. This may be an example of heterosis.