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).

Conclusion: 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.