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Polymorphisms in complement component 3 (C3F) and complement factor H (Y402H) increase the risk of postoperative neurocognitive dysfunction following carotid endarterectomy
  1. Paul R Gigante1,
  2. Ivan S Kotchetkov1,
  3. Christopher P Kellner1,
  4. Raqeeb Haque1,
  5. Andrew F Ducruet1,
  6. Brian Y Hwang1,
  7. Robert A Solomon1,
  8. Eric J Heyer2,
  9. E Sander Connolly1
  1. 1Department of Neurological Surgery, Columbia University, College of Physicians & Surgeons, New York, USA
  2. 2Department of Anaesthesiology, Columbia University, College of Physicians & Surgeons, New York, USA
  1. Correspondence to Dr Paul R Gigante, Department of Neurological Surgery, Columbia University, College of Physicians & Surgeons, 630 West 168th Street, New York, NY 10032, USA; pg2223{at}


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).

Conclusion 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.

  • Carotid endarterectomy
  • carotid stenosis
  • polymorphism
  • complement factor H
  • complement component 3
  • genetics
  • neurosurgery
  • stroke
  • vascular surgery

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  • Funding ESC was supported in part by Grant Number R01-NS-040409-08 from the National Institutes of Health (NIH) and the Department of Neurological Surgery, Columbia University; New York, NY. EJH was supported in part by Grant Number R01-AG-017604-06 from the NIH and the Department of Anesthesiology, Columbia University; New York, NY. The Columbia Irving CTSA Program was supported by Grant Number UL1 RR024156 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. The contents of this project are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the Columbia University Medical Center Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.