Complement polymorphisms and cognitive dysfunction after carotid endarterectomy

Abstract

Object The role of genetic polymorphisms in the neurological outcome of patients after carotid endarterectomy (CEA) remains unclear. There are single nucleotide polymorphisms (SNPs) that predispose patients to postoperative cognitive dysfunction (CD). We aim to assess the predictability of three complement cascade-related SNPs for CD in patients having CEAs. Methods In 252 patients undergoing CEA, genotyping was performed for the following polymorphisms: complement component 5 (C5) rs17611, mannose-binding lectin 2 (MBL2) rs7096206, and complement factor H (CFH) rs1061170. Differences among genotypes were analyzed via the chi-square test. Patients were evaluated with a neuropsychometric battery for CD 1 day and 1 month after CEA. A multiple logistic regression model was created. All variables with univariate p < 0.20 were included in the final model. Results The C5 genotypes A/G (OR 0.26, 95% CI 0.11–0.60, p = 0.002) and G/G (OR 0.22, 95% CI 0.09–0.52, p < 0.001) were significantly associated with lower odds of exhibiting CD at 1 day after CEA compared with A/A. The CFH genotypes C/T (OR 3.37, 95% CI 1.69–6.92, p < 0.001) and C/C (OR 3.67, 95% CI 1.30–10.06, p = 0.012) were significantly associated with higher odds of exhibiting CD at 1 day after CEA compared with T/T. Statin use was also significantly associated with lower odds of exhibiting CD at 1 day after CEA (OR 0.43, 95% CI 0.22–0.84, p = 0.01). No SNPs were significantly associated with CD at 1 month after CEA. Conclusions The presence of a deleterious allele in the C5 and CFH SNPs may predispose patients to exhibit CD after CEA. This finding supports previous data demonstrating that the complement cascade system may play an important role in the development of CD. These findings warrant further investigation.