Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients
| Autor: | Hans O. Madsen, Jørn Wetterslev, Jørgen Wiis, Dorthe Hellemann, Torsten Faber, Jens Otto Jarløv, Anders Larsson, Jan Bonde, Peter Garred |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Heterozygote Adolescent Critical Illness Biology Gastroenterology Mannose-Binding Lectin law.invention Loss of heterozygosity Gene Frequency law Intensive care Internal medicine Sepsis Genotype Genetics medicine Hybrid Vigor Humans Molecular Biology Allele frequency Genetics (clinical) Mannan-binding lectin Aged Aged 80 and over Hazard ratio Case-control study General Medicine Middle Aged Prognosis Intensive care unit Patient Discharge Intensive Care Units Case-Control Studies Immunology Female Algorithms |
| Zdroj: | Hellemann, D, Larsson, A, O. Madsen, H, Bonde, J, Jarløv, J O, Wiis, J, Faber, T, Wetterslev, J & Garred, P 2007, ' Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients ', Human Molecular Genetics, pp. 3071-3080 . |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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