There Is No Association Between the Circadian Clock Gene HPER3 and Cognitive Dysfunction After Noncardiac Surgery

May 1, 2012Anesthesia and analgesia

No link between the body’s daily rhythm gene HPER3 and thinking problems after non-heart surgery

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Abstract

Among 279 patients, 12% had the PER3(5/5) genotype, with no significant association to postoperative cognitive dysfunction (POCD) at 1 week.

The study included patients aged 40 years and older undergoing noncardiac surgery.
Three genotypes were identified: 11.8% PER3(5/5), 41.7% PER3(4/5), and 46.5% PER3(4/4).
No significant difference in genotype distribution was observed between patients with and without POCD (P = 0.68).
The incidence difference of POCD between patients with and without the PER3(5/5) genotype was 1% (-7% to 10%).
Patients with the PER3(4/4) genotype showed a significantly higher Z score in one neuropsychological test.

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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.

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There Is No Association Between the Circadian Clock Gene HPER3 and Cognitive Dysfunction After Noncardiac Surgery

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