Prospective Analysis of Mannose-Binding Lectin Genotypes and Coronary Artery Disease in American Indians

Abstract

Background-Mannose-binding lectin (MBL) is a circulating immune factor responsible for opsonization of pathogens and directly activating complement. Common variations in the MBL gene are responsible for an opsonic deficiency that affects 5% to 7% of whites and are associated with increased susceptibility to infections. After a preliminary report associating these variations with coronary artery disease (CAD), we determined MBL genotypes in 3 American Indian communities experiencing an increased mortality and morbidity from CAD. Methods and Results-We examined DNA from 434 participants in a population-based cohort, the Strong Heart Study.Genotypes for 3 common MBL coding variations and 1 promoter polymorphism were determined.

Genetically determined high serum levels of mannose-binding lectin and agalactosyl IgG are associated with ischemic heart disease in rheumatoid arthritis

“…In contrast to these observations, MBL variant alleles resulting in dysfunctional MBL or lack of MBL have been reported to be associated with accelerated atherosclerosis and cardiovascular occlusion in other patient groups (9)(10)(11)(12)(13). This paradox is probably a key issue in the understanding of the role of MBL in human disease.…”

“…Lack of functional alleles in some populations is associated with increased risk of atherosclerosis and cardiovascular occlusion (9)(10)(11)(12)(13). However, experimental data and clinical observations suggest that MBL and the lectin pathway of complement may initiate the inflammatory reaction seen in relation to ischemia reperfusion injury (14)(15)(16).…”

Cholesterol Crystals Activate the Lectin Complement Pathway via Ficolin-2 and Mannose-Binding Lectin: Implications for the Progression of Atherosclerosis

“…Several population-based studies, analyzing either MBL genotypes or resulting serum levels, suggest a role for MBL in cardiovascular disease (34,(52)(53)(54)(55)(56)(57)(58). However, the results are contradictory, suggesting either a proatherogenic or antiatherogenic role of MBL in cardiovascular disease.…”

Mannose-Binding Lectin in Obesity with Different Degrees of Metabolic Syndrome Abnormalities: Association with Atherogenic and Metabolic Traits

“…Many complement components play an important role in the progression and maturation of atherosclerotic lesions 7,8) , and the complement component C3 is additionally related to insulin resistance 9,10) . Common variant MBL genotypes, coding for markedly diminished levels of MBL, have been shown to be predictive of coronary artery disease (CAD) and severe atherosclerosis, even after adjustment for traditional cardiovascular risk factors [11][12][13] . MBL deficiency also appeared to be associated with venous bypass graft occlusions in patients with coronary heart disease 14) .…”

“…Separating individuals with low and high MBL levels did also not reveal an association with the Contradictory data for MBL are also available with respect to atherosclerosis and coronary disease. Common variant MBL genotypes, coding for markedly diminished levels of MBL, have been shown to be predictive of coronary artery disease and severe atherosclerosis, even after adjustment for traditional cardiovascular risk factors [11][12][13] . Contrary to these findings, it has been documented that a high MBL level may be a risk factor for acute coronary syndromes 15) and future coronary artery disease 16) , and that functional MBL deficiency contributes to reduced mortality in patients patients 19) .…”