Genetic variation in complement factor H and risk of coronary heart disease: eight new studies and a meta-analysis of around 48,000 individuals.
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.
Sofat
Reecha
R
Centre for Clinical Pharmacology, Division of Medicine, University College London, Rayne Building, 5 University Street, London WC1E 6JF, UK. r.sofat@ucl.ac.uk
Casas
Juan P
JP
Kumari
Meena
M
Talmud
Philippa J
PJ
Ireland
Helen
H
Kivimaki
Mika
M
Marmot
Michael
M
Hughes
Alun D
AD
Thom
Simon
S
Ebrahim
Shah
S
Whittaker
John C
JC
Smeeth
Liam
L
Lawlor
Debbie A
DA
Humphries
Steve E
SE
Hingorani
Aroon D
AD
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
D014280:Triglycerides; D017242:Complement Factor H