Polymorphisms in complement component 3 (C3F) and complement factor H (Y402H) increase the risk of postoperative neurocognitive dysfunction following carotid endarterectomy.
BACKGROUND
Up to 28% of patients undergoing carotid endarterectomy (CEA) are estimated to experience neurocognitive dysfunction following surgery. The complement cascade plays a central role in ischaemia-reperfusion injury. The authors investigated the effect of common polymorphisms in the complement component 3 (C3F) and complement factor H (CFH Y402H) genes on incidence of neurocognitive dysfunction post-CEA.


METHODS
This study examined a nested cohort of prospectively recruited patients receiving elective CEA, who were genotyped for the C3F or Y402H polymorphisms. Each patient underwent a standard battery of eight neuropsychometric tests before, and 1 day and 30 days after, surgery.


RESULTS
57 of 142 (40%) CEA patients had at least one copy of the C3F allele (C3F+), and 17 of 137 (12%) patients had two copies of the CFH Y402H allele (Y402H++). At postoperative day 1, patients were three times (OR 3.05, p=0.045) or six times (OR 6.41, p=0.006) more likely to experience moderate-to-severe neurocognitive dysfunction if they carried the C3F+ or Y402H++ genotype, respectively. Patients with both risk genotypes had an almost eightfold risk of dysfunction (OR 7.67, p=0.046). Right-hand-dominant C3F+ subjects undergoing right-side CEA performed significantly worse on tests of visuospatial function than C3F- subjects. At day 30, C3F+ and Y402H++ genotypes trended towards significance as predictors of dysfunction (p=0.07 and p=0.22, respectively).


CONCLUSIONS
The C3F and Y402H polymorphisms are strong independent predictors of moderate-to-severe neurocognitive dysfunction at 1 day following CEA. Furthermore, patients undergoing right-sided CEA are predisposed to deficits associated with cortex ipsilateral to the operative carotid artery.
Gigante
Paul R
PR
Department of Neurological Surgery, Columbia University, College of Physicians & Surgeons, 630 West 168th Street, New York, NY 10032, USA. pg2223@columbia.edu
Kotchetkov
Ivan S
IS
Kellner
Christopher P
CP
Haque
Raqeeb
R
Ducruet
Andrew F
AF
Hwang
Brian Y
BY
Solomon
Robert A
RA
Heyer
Eric J
EJ
Connolly
E Sander
ES
D000368:Aged; D000483:Alleles; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics; D003176:Complement C3 / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D016894:Endarterectomy, Carotid / Q000009:adverse effects*; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D015427:Reperfusion Injury / Q000209:etiology / Q000235:genetics; D012307:Risk Factors
C493495:CFH protein, human; D003176:Complement C3; D017242:Complement Factor H