| Background:Postoperative cognitive dysfunction( POCD) is a common postoperative complication that occurs after major surgeries, most notably, cardiac surgery. The symptoms of POCD include deliriousness, anxiety, change of character and impairments in memory. This disorder may last from a few days to a few weeks after surgery. In rare cases, it may persist for several months or longer. POCD exists after both cardiac and non-cardiac surgery. Some studies show that heart surgery, especially with cardiopulmonary bypass, is causally associated with a high risk of POCD, maybe up to 83%. POCD increases other postoperative complications, case fatality rate, length of stay and medical cost, and reduces the quality of life. Thus, POCD has aroused extensive attention around the world. The etiology of perioperative neurologic injury is multifactorial, but preliminary researches of heritability of cognitive decline suggest that genetic factors may modulate response to this type of neurologic injury. Some researchers hypothesized that single nucleotide polymorphism(SNP) regulate the susceptibility of POCD. Usually, one or several candidate genes were chosen, and then the correlation between the genes and the incidence of POCD was explored. No one had yet investigated the SNPs in the whole genome associated with POCD with the method of Genome Wide Association Studies(GWAS). Hence, we design the following trial. Objective:1. Evaluate the postoperative cognition of the paitients over age 60, whoundergo cardiac surgery with CPB, and take their DNA samples for GWAS.Screen out the SNPs associated with POCD.2. Analysis the correlation of candidate SNPs and POCD, and prepare for thefurther studies. Method:The patients over age 60 who would undergo cardiac surgery with CPB were selected. After completed the preoperative examination and preparation of the patients, we assessed their cognitive function with Mini-Mental State Examination(MMSE) on the day before surgery and again on the 7th postoperatively. Meanwhile 4ml blood was taken from the patient on the day before surgery and dissolved in ethylenediaminetetraacetic acid(EDTA) buffer at-80℃ for analysis. All the patients were divided into POCD group and non-POCD group by MMSE scores. DNA was extracted from the blood samples and tested by gene chips. Then, we examined all the detected SNPs whether consistent with Hardy-Weinberg equilibrium, and filtered out the SNPs with Hardy-Weinberg P value(Hwpval) <0.05, and minor allele frequency(MAF)<0.05. After P-values for the significance of the odds ratios had been calculated for all SNPs, 50 SNPs with the smallest P values were chosen for further inquiry of locations and functions. At last, the genes and SNPs most likely to affect POCD were selected. Results:A total of 65 patients were included in the final test and analysis,20 of them suffered with POCD, and other 45 patients not. Baseline characteristics including age, height, weight, preoperative MMSE scores, smoke and other accompanied diseases were similar between groups(P>0.05), except for the proportion of male patients, which was statistically significantly larger in POCD group. After data quality control and correlation analysis, 50 SNPs with the smallest P values were chosen from the total of 93,994 SNPs detected by gene chips. Query the information of these SNPs and their genes through the websites( http://www.hapmap.org 、 http://www.ncbi.nlm.nih.gov/snp and http://www.genecards.org). At last, rs9311419, rs1822223, rs4685835 in ITPR1 and rs7919846 in CDH23 were selected more likely to impact the incidence of POCD. Conclusion:SNP is the genetic factor influencing the occurrence of POCD, of which rs9311419、rs1822223、rs4685835 in ITPR1 gene and rs7919846 in CDH23 are more likely to impact the incidence of POCD. |
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