There is no association between the circadian clock gene HPER3 and cognitive dysfunction after noncardiac surgery

BACKGROUND: The specific clock-gene PERIOD3 is important with regard to circadian rhythmicity, sleep homeostasis, and cognitive function. The allele PER3 ^5/5 has been associated with worse cognitive performance in response to sleep deprivation. We hypothesized that patients with the PER3 ^5/5 genotype would have an increased risk of postoperative cognitive dysfunction (POCD) 1 week after noncardiac surgery. METHODS: Blood samples were analyzed from 93 patients with POCD and 186 patients without POCD from a completed multicenter study. The study population comprised patients ages 40 years and older undergoing noncardiac surgery who were tested preoperatively and 1 week after surgery with a neuropsychological test battery comprising 7 subtests. PER3 genotypes were determined by polymerase chain reaction analysis of DNA from blood samples (Clinicaltrials.gov identifier NCT01088100). RESULTS: The frequencies of the 3 genotypes were 11.8% (32 patients) PER3 ^5/5, 41.7% (113 patients) PER3 ^4/5, and 46.5% (126 patients) PER3 ^4/4. No significant difference was found in the distribution of the 3 genotypes according to POCD at 1 week (P = 0.68). Twelve percent (6% to 21%) of the patients with POCD and 12% (7% to 17%) of the patients without POCD had the PER3 ^5/5 genotype. The difference of the incidence of POCD/-POCD for the PER3 ^5/5 genotype was 1% (-7% to 10%). A significantly higher Z score was found in patients having the PER3 ^4/4 in 1 of the neuropsychological tests (error score of the Concept Shifting Test) (Bonferroni corrected P = 0.042). CONCLUSION: No significant association was found between the clock-gene PER3 ^5/5 genotype and POCD at 1 week after noncardiac surgery. If PER3 ^5/5 does worsen cognitive performance, the incidence is <10% of patients.