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.

Beyond C4: Analysis of the complement gene pathway shows enrichment for IQ in patients with psychotic disorders and healthy controls

“…However, we did not have a specific hypothesis around this aspect of cognitive performance, and instead interpret the data to indicate a broad association with each of the measures available, depending of the sensitivity of each measure used. The direction of this association is interesting given multiple previous reports that upregulation of complement genes (theoretically driving increased neuroinflammation and synaptic pruning) to be associated with cognitive decline . In enrichment analysis, genes related to the phenotype of IQ (SERPING1, CD46) tended to be regulators of the complement system, thus our PGS may represent regulatory activities of the complement cascade, inhibiting inappropriate activation of complement and inflammatory processes .…”

MBL2 gene polymorphisms increase the risk of adverse neurological outcome in preterm infants: a preliminary prospective study

“…Our data add to the knowledge about genetic predisposition to more severe neurological outcomes of prematurity, which may be a marker of individual weakness. (22) in a recent study, explored the relationship between the G/C SNP of the MBL2 gene and cognitive disfunction (CD) after carotid endoarterectomy (CEA) in 252 adult patients. The replacement of G by C in the promoter region of the MBL2 gene on chromosome 10 leads to an X to Y amino acid change resulting in a low expression of MBL2 and reduced serum concentration in the range of a 25-50% decrease per deleterious allele.…”

Neutrophil-lymphocyte ratio as a predictor of cognitive dysfunction in carotid endarterectomy patients

“…Systemic inflammation has been implicated in the progression of atherosclerosis and plaque instability 10 . Genetic mutations linked to systemic inflammation 11, 12 and elevated inflammatory markers like monocyte count 6 and monocyte chemoattractant protein 13 , are significantly associated with cognitive dysfunction after CEA.…”