title: Mannose-binding lectin deficiency is associated with myocardial infarction: the HUNT2 study in Norway.
abstract: OBJECTIVE
  Mannose-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.
  
  
  RESULTS
  Using the population-based HUNT Study in Norway, 57,133 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.
  
  
  CONCLUSIONS
  In 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.
authors: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology. Trondheim, Norway.
authors: Inga Thorsen
authors: IT
authors: Vengen
authors: Hans O
authors: HO
authors: Madsen
authors: Peter
authors: P
authors: Garred
authors: Carl
authors: C
authors: Platou
authors: Lars
authors: L
authors: Vatten
authors: Vibeke
authors: V
authors: Videm
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D037601:Mannose-Binding Lectin / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D009664:Norway / Q000453:epidemiology; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D037601:Mannose-Binding Lectin