Abstract 459: The Impact of Mannose Binding Lectin Gene Polymorphisms on Endothelial Function in Childhood
Background: Infection has been implicated in endothelial dysfunction in childhood. Variants in mannose binding lectin (MBL; an integral component of innate immunity) gene are tightly associated with circulating levels of this protein. Deficiency in MBL is associated with increased susceptibility and severity of infections in children and increased cardiovascular events in adults. However the role of this protein in the vascular biology of atherosclerosis remains largely unknown. We therefore assessed the influence of MBL genotype on endothelial function in the presence and absence of infection in childhood.
Methods: We studied 2000 children aged 10yrs drawn from the Avon Longitudinal Study of Parents and Children. Endothelial function was assessed by measuring brachial artery flow mediated dilatation (FMD) using high resolution ultrasound. Exon 1 and promoter polymorphisms in the MBL gene were determined by heteroduplexing procedures. Children were classified in group 1(wild type) group 2 (heterozygotes) and group 3 (homozygotes) that have normal, intermediate and low or absent MBL levels respectively.
Results: Genotypic information existed for 1719 children. At the time of vascular study 414 of these children presented with current or recent (<2weeks) infection (INF). FMD was reduced in the INF group compared to controls (p<0.001). Cardiovascular risk factor profile was similar in groups 1–3. MBL was not associated with FMD in healthy children, however a relationship with the degree of impairment during INF was observed (9.7%, 9.6% and 24.8% fall in FMD for groups 1–3 respectively, p<0.05). Additionally, group 3 was a predictor of an impaired FMD (lowest quartile) during infection (odds ratio[95%CI] 4.0[1.4, 11.9] p<0.01). After multiple regression analysis, homozygosity for MBL remained the only independent predictor of reduced FMD with INF(2.6[1.1, 6.6] p<0.05).
Conclusion: Homozygosity for MBL variant allele, predictive of low MBL levels, is associated with greater impairment in endothelial function during infection in childhood, suggesting a gene-environment interaction operating early in life. The long-term impact of MBL genotype on arterial disease progression requires further study.