Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients.
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. Five hundred and thirty-two consecutive critically ill patients admitted to an intensive care unit (ICU) were included over a period of 18 months. Five hundred and thirty-three 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, whereas 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 whereas homozygosity is associated with the worst outcome soon after discharge from ICU. This may be an example of heterosis.
Hellemann
Dorthe
D
Department of Anaesthesiology and Intensive Care, Herlev, Copenhagen University Hospital, Rigshospitalet, Denmark.
Larsson
Anders
A
Madsen
Hans O
HO
Bonde
Jan
J
Jarløv
Jens Otto
JO
Wiis
Jørgen
J
Faber
Torsten
T
Wetterslev
Jørn
J
Garred
Peter
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D016022:Case-Control Studies; D016638:Critical Illness / Q000401:mortality*; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D006823:Hybrid Vigor / Q000235:genetics / Q000502:physiology*; D007362:Intensive Care Units; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D010351:Patient Discharge; D011379:Prognosis; D018805:Sepsis / Q000235:genetics* / Q000401:mortality
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin