title: Genetic variation in complement factor H and risk of coronary heart disease: eight new studies and a meta-analysis of around 48,000 individuals.
abstract: OBJECTIVE
  To investigate the association of polymorphisms in complement factor H (CFH) and coronary heart disease (CHD) using meta-analysis.
  
  
  BACKGROUND
  Age-related macular degeneration (AMD) and CHD may share partially overlapping pathogenesis. A non-synonymous SNP (rs1061170/Y402H) in CFH encoding complement factor H (fH) is robustly associated with increased AMD risk but associations with CHD risk have been inconsistent.
  
  
  METHODS
  We conducted de novo genotyping and genetic association analyses of incident and prevalent CHD in four studies, and in silico analysis of the same association in a further four cohorts. We pooled these data with information from all published studies using random effects meta-analysis, including a total of 48,646 participants of which 9097 were CHD cases. We also evaluated the association of Y402H with known risk factors for CHD by pooling results from new and in silico studies providing relevant data.
  
  
  RESULTS
  CFH genotype was not associated with CHD. Compared to the reference TT homozygote group the pooled odds ratio (OR) for individuals homozygous for the C allele was 1.02, 95% CI (0.91, 1.13) and that for heterozygote TC individuals was 1.04 (0.98, 1.10). There was no association of CFH with systolic and diastolic blood pressure, total-, LDL- and HDL-cholesterol, or body mass index. Individuals who were CC compared to TT had higher triglyceride levels: pooled mean difference 0.06 (0.02, 0.10) mmol/L, p=0.005.
  
  
  CONCLUSIONS
  The AMD-associated CFH genotype is not associated with CHD. With the possible exception of triglycerides, this CFH SNP was not associated with a wide range of other CHD risk factors.
authors: Centre for Clinical Pharmacology, Division of Medicine, University College London, Rayne Building, 5 University Street, London WC1E 6JF, UK. r.sofat@ucl.ac.uk
authors: Reecha
authors: R
authors: Sofat
authors: Juan P
authors: JP
authors: Casas
authors: Meena
authors: M
authors: Kumari
authors: Philippa J
authors: PJ
authors: Talmud
authors: Helen
authors: H
authors: Ireland
authors: Mika
authors: M
authors: Kivimaki
authors: Michael
authors: M
authors: Marmot
authors: Alun D
authors: AD
authors: Hughes
authors: Simon
authors: S
authors: Thom
authors: Shah
authors: S
authors: Ebrahim
authors: John C
authors: JC
authors: Whittaker
authors: Liam
authors: L
authors: Smeeth
authors: Debbie A
authors: DA
authors: Lawlor
authors: Steve E
authors: SE
authors: Humphries
authors: Aroon D
authors: AD
authors: Hingorani
mesh_terms: D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics*; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D009203:Myocardial Infarction / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood
chemical_list: D014280:Triglycerides; D017242:Complement Factor H