Infection-susceptibility alleles of mannose-binding lectin are associated with increased carotid plaque area

Abstract

The MBL gene, encoding mannose-binding lectin, determines interindividual variation in susceptibility to certain infectious agents, such as Chlamydia pneumoniae. We examined whether infection-susceptibility alleles of MBL, called "non-A alleles," would be associated with increased carotid plaque area (CPA), an intermediate phenotype of atherosclerosis. 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 variation for CPA and tested the hypothesis that the presence of a single MBL non-A "infection-susceptibility" allele was associated 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 association 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 sample; these alleles may be a determinant of interindividual differences in atherosclerosis risk.