Complement factor H Y402H decreases cardiovascular disease risk in patients with familial hypercholesterolaemia.
OBJECTIVE
Activation of the complement system seems an important link between inflammation and atherogenesis. The Y402H polymorphism of complement factor H (CFH) has been associated with cardiovascular events, but results are conflicting and possibly modified by age of onset of cardiovascular disease (CVD).


RESULTS
We determined whether or not the Y402H polymorphism influenced CVD risk in a multicentre cohort study involving 2,016 unrelated patients with familial hypercholesterolaemia (FH), who have an extremely increased susceptibility to premature CVD. We identified 261 individuals who were homozygous for the polymorphism (CC genotype; 12.9%), 929 individuals who were heterozygous (TC genotype; 46.1%), and 826 individuals carried the wild-type (TT genotype; 41.0%). During 95 115 person years, 644 patients had a cardiovascular event. Carriers of the CC genotype had a decreased risk of CVD (hazard ratio 0.67, 95% confidence interval 0.51-0.87; P = 0.003) relative to the other genotype groups. This association was unaltered after adjustment for clinically relevant cardiovascular risk factors or age effects.


CONCLUSIONS
Among patients with severely increased risk of early onset CVD, the Y402H CFH variant was inversely associated with susceptibility to CVD. This suggests that CFH is a modifier gene of CVD.
Koeijvoets
Kristel C M C
KC
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Mooijaart
Simon P
SP
Dallinga-Thie
Geesje M
GM
Defesche
Joep C
JC
Steyerberg
Ewout W
EW
Westendorp
Rudi G J
RG
Kastelein
John J P
JJ
van Hagen
P Martin
PM
Sijbrands
Eric J G
EJ
D000328:Adult; D000367:Age Factors; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics*; D004812:Epidemiologic Methods; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis
D017242:Complement Factor H