Endothelial response to childhood infection: the role of mannose-binding lectin (MBL).
OBJECTIVE
To assess the influence of mannose-binding lectin (MBL) genotype on endothelial function in the presence and absence of infection in childhood.


METHODS
We studied 2176 children aged 10 years drawn from the Avon Longitudinal Study of Parents and Children. Endothelial function was assessed by flow mediated dilatation (FMD). Exon 1 and promoter polymorphisms in the MBL gene were determined by heteroduplexing procedures. Children were classified as AA (wild type) AO (heterozygotes) and OO (homozygotes).


RESULTS
During the vascular assessment, 544 children presented with current or recent (<2 weeks) infection (INF). FMD was reduced in the INF group compared to controls (10% reduction in FMD, p<0.001). MBL genotype was not associated with FMD in controls, although a relationship with the degree of impairment during INF was observed (8.0%, 7.6% and 26.6% lower FMD compared to controls for groups AA, AO, OO respectively, p<0.05). After multivariate analysis, OO was associated with reduced FMD in the INF group (odds ratio 2.95 [1.33, 6.52], p<0.001).


CONCLUSIONS
Homozygosity for MBL variant alleles is associated with greater impairment in FMD during infection in childhood. This suggests a gene-environment interaction operating in early life that may have relevance for the initiation and progression of atherosclerosis.
Charakida
Marietta
M
Vascular Physiology Unit, Institute of Child Health, University College London, 34 Great Ormond Street, London, UK. charakidadoc@hotmail.com
Donald
Ann E
AE
Leary
Sam
S
Halcox
Julian P
JP
Turner
Malcolm W
MW
Johnson
Marina
M
Loukogeorgakis
Stavros P
SP
Okorie
Michael I
MI
Davey Smith
George
G
Deanfield
John E
JE
Klein
Nigel J
NJ
D002648:Child; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005838:Genotype; D006801:Humans; D007239:Infections / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D011110:Polymorphism, Genetic
D037601:Mannose-Binding Lectin