Infection-Susceptibility Alleles of Mannose-Binding Lectin are Associated with Increased Carotid Plaque Area

Abstract

The MBL gene, encoding mannose-binding lectin, deter- mines interindividual variation in susceptibility to certain infectious agents, such as Chlamydia pneumoniae. We exam- ined whether infection-susceptibility alleles of MBL, called “non-A alleles,” would be associated with increased carotid plaque area (CPA), an intermediate phenotype of atheroscle- rosis. In 164 subjects, we measured CPA with 2-dimensional ultrasound. We also determined traditional atherosclerosis risk factors and genotyped all subjects for MBL codons 52, 54, and 57. We used ANOVA to determine sources of varia- tion for CPA and tested the hypothesis that the presence of a single MBL non-A “infection-susceptibility” allele was asso- ciated with increased CPA; 45.7% of subjects had at least one non-A allele. ANOVA showed that CPA was significantly associated with MBL genotype, age, smoking, hypertension, and hyperlipidemia (P<0.05). When MBL was used as the sole independent variable in the regression analysis, the as- sociation with CPA was even more significant (P=0.009). Subjects with at least one MBL non-A allele had significantly higher CPA than subjects homozygous for the MBL A allele and were significantly more likely to have CPA in excess of the sample median. Thus, infection-susceptibility alleles of MBL were associated with increased CPA in this study sam- ple; these alleles may be a determinant of interindividual differences in atherosclerosis risk.