Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients.
Hum Mol Genet
; 16(24): 3071-80, 2007 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-17872904
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estado Terminal
/
Sepse
/
Lectina de Ligação a Manose
/
Heterozigoto
/
Vigor Híbrido
/
Unidades de Terapia Intensiva
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Dinamarca