Mannose-Binding Lectin Deficiency Is Associated with Myocardial Infarction: The HUNT2 Study in Norway

Abstract

ObjectivesMannose-binding lectin (MBL) and ficolins activate the complement cascade, which is involved in atherogenesis. Based on a pilot study, we hypothesized that functional polymorphisms in the MBL gene (MBL2) leading to dysfunctional protein are related to development of myocardial infarction (MI). The aim of the present study was to study polymorphisms in MBL2 and ficolin genes in relation to the risk of MI.Methods and ResultsUsing the population-based HUNT Study in Norway, 57133 persons were followed up for a first-time MI from 1995–1997 until the end of 2008. The 370 youngest MI patients were matched by age (range 29–62 years) and gender to 370 controls. A younger population was selected because disease in this group might be less dependent on non-genetic risk factors. The study size was based on power calculation. Polymorphisms in MBL2 and in the genes of ficolin-1, ficolin-2 and ficolin-3 were genotyped by pyrosequencing and related to the risk of MI, estimated as odds ratios (OR). Functional haplotypes were analyzed and stringent alpha levels of significance were set by permutation testing. Variant MBL2 haplotypes causing MBL deficiency were associated with a two-fold higher risk of MI (OR 2.04, 95%CI 1.29–3.24). Adjustments for conventional cardiovascular risk factors did not substantially influence the association. The ficolins were not associated with MI risk.ConclusionIn a young to middle aged and relatively healthy Caucasian population, MBL2 variants related to functional MBL deficiency were associated with a doubling of the risk for MI, independent of conventional risk factors. This supports that MBL deficiency may lead to increased atherosclerosis or development of vulnerable plaques.

Biological role of mannose binding lectin: From newborns to centenarians

“…Opposite results were found by other studies: a prospective observation of about 20,000 subjects demonstrated a lower risk for myocardial infarction in subjects with high serum levels of MBL [32], and a higher occurrence of MBL deficiency was found in patients that experienced AMI [33].…”

A vital role for complement in heart disease

“…Alipour et al did not find any association between MBL2 haplotypes and the progression of coronary heart disease in statin treated patients (Alipour et al, 2011). Vengen et al have found that MBL2 gene variants with functional MBL deficiency were associated with increased risk for myocardial infarction in a population-based cohort of young individuals followed for 10 years (Vengen et al, 2012). Leban et al recently described a strong relationship between the C3F allele of the C3 gene, coding for complement factor C3 of the common pathway, and risk of myocardial infarction (Leban et al, 2013).…”

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

“…Whether the LP is involved in the local inflammation initiated by CC in the pathophysiology of atherosclerosis is not known, but MBL is present in atherosclerotic lesions, and MBL gene variants leading to functional defects of MBL have been associated with myocardial infarction (33) and severity of atherosclerosis (34,35). Cholesterol compounds have been shown to differ in their complement activation ability, depending on the position as well as the number of hydroxyl groups (4).…”