title: Complement receptor 1 gene polymorphisms are associated with cardiovascular risk.
abstract: Inflammation plays a key role in atherosclerosis. The complement system is involved in atherogenesis, and the complement receptor 1 (CR1) plays a role facilitating the clearance of immune complexes from the circulation. Limited evidence suggests that CR1 may be involved in cardiovascular disease. We investigated the relationship between CR1 gene polymorphisms and cardiovascular risk.
  
  
  
  Single nucleotide polymorphisms (SNPs) within the CR1 region (n = 73) on chromosome 1 were assessed in 5244 participants in PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) (mean age 75.3 years), who had been randomized to pravastatin 40 mg/day or placebo and followed for a mean of 3.2 years. Logistic regression, adjusted for gender, age, country and use of pravastatin, was used to assess the association between the SNPs and cardiovascular disease.
  
  
  
  All 73 SNPs within the genomic region of the CR1 gene on chromosome 1 were extracted. In this region, strong LD was present leading to the occurrence of two haploblocks. Twelve of the 73 investigated CR1 SNPs were significantly associated with the risk of fatal or nonfatal myocardial infarction (all p < 0.05). Moreover, most of the associated SNPs were also associated with levels of serum C-reactive protein (CRP). The global p-value for the tail strength method to control for multiple testing was 0.0489, implying that the null hypothesis of no associated SNPs can be rejected.
  
  
  
  These data indicate that genetic variation within the CR1 gene is associated with inflammation and the risk of incident coronary artery disease.
authors.affiliation: Department of Internal Medicine, Center for Diabetes and Vascular Medicine, Franciscus Gasthuis, Rotterdam, The Netherlands. Electronic address: m.devries@sfg.nl.
authors.forename: Marijke A
authors.initials: MA
authors.lastname: de Vries
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Institute of Evidence Based Medicine at Old Age, Leiden, The Netherlands.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mooijaart
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Roelof A J
authors.initials: RA
authors.lastname: Smit
authors.affiliation: Department of Medical Biostatistics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Böhringer
authors.affiliation: Department of Internal Medicine, Center for Diabetes and Vascular Medicine, Franciscus Gasthuis, Rotterdam, The Netherlands.
authors.forename: Manuel
authors.initials: M
authors.lastname: Castro Cabezas
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017463:Receptors, Complement 3b / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C509991:CR1 protein, human; D018836:Inflammation Mediators; D017463:Receptors, Complement 3b; D002097:C-Reactive Protein
keywords: Apolipoprotein B; Atherosclerosis; C-reactive protein; Inflammation; Myocardial infarction