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Phosphodiesterase 4D single-nucleotide polymorphism 83 and cognitive dysfunction in carotid endarterectomy patients.

ABSTRACT: Phosphodiesterase 4D (PDE4D), through the regulation of cyclic AMP, modulates inflammation and other processes that affect atherosclerosis and stroke. A PDE4D polymorphism, single-nucleotide polymorphism (SNP) 83 (rs966221), is associated with ischemic stroke. The association of SNP 83 with postoperative cognitive dysfunction has never been investigated.To determine whether SNP 83 is associated with cognitive dysfunction 1 day and 1 month following carotid endarterectomy (CEA).Three hundred fourteen patients with high-grade carotid stenosis scheduled for CEA consented to participate in this single-center cohort study of cognitive dysfunction.Patients with the C/C genotype of SNP 83 exhibited significantly more cognitive dysfunction at 1 day (29.7%) than the C/T (15.8%, P = .008) and T/T (12.7%, P = .01) genotypes. In a multivariate logistic regression model, C/T and T/T genotypes were both associated with significantly decreased odds of cognitive dysfunction compared with the C/C genotype (odds ratio, 0.45 [0.24-0.83], P = .01 and odds ratio, 0.33 [0.12-0.77], P = .02). There were no significant associations at 1 month.The C/C genotype of SNP 83 is significantly associated with the highest incidence of cognitive dysfunction 1 day following CEA in comparison with the C/T and T/T genotypes. This PDE4D genotype may lead to accelerated cyclic AMP degradation and subsequently elevated inflammation 1 day after CEA. These observations, in conjunction with previous studies, suggest that elevated inflammatory states may be partially responsible for the development of cognitive dysfunction after CEA, but more investigation is required.

SUBMITTER: Heyer EJ

PROVIDER: S-EPMC3935380 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Phosphodiesterase 4D single-nucleotide polymorphism 83 and cognitive dysfunction in carotid endarterectomy patients.

Heyer Eric J EJ Mergeche Joanna L JL Ward Justin T JT Malone Hani R HR Kellner Christopher C Bruce Samuel S SS Connolly E Sander ES

Neurosurgery 20131101 5

<h4>Background</h4>Phosphodiesterase 4D (PDE4D), through the regulation of cyclic AMP, modulates inflammation and other processes that affect atherosclerosis and stroke. A PDE4D polymorphism, single-nucleotide polymorphism (SNP) 83 (rs966221), is associated with ischemic stroke. The association of SNP 83 with postoperative cognitive dysfunction has never been investigated.<h4>Objective</h4>To determine whether SNP 83 is associated with cognitive dysfunction 1 day and 1 month following carotid en ...[more]

PMID: 23863764

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Project description:BACKGROUND: The phosphodiesterase 4D (PDE4D) gene was reported as a susceptibility gene to stroke. The genetic effect might be attributed to its role in modulating the atherogenic process in the carotid arteries. Using carotid intima-media thickness (IMT) and plaque index as phenotypes, the present study sought to determine the influence of this gene on subclinical atherosclerosis. METHODS: Carotid ultrasonography was performed on 1013 stroke-free subjects who participated in the health screening programs (age 52.6 +/- 12.2; 47.6% men). Genotype distribution was compared among the high-risk (plaque index > or = 4), low-risk (index = 1-3), and reference (index = 0) groups. We analyzed continuous IMT data and further dichotomized IMT data using mean plus one standard deviation as the cutoff level. Because the plaque prevalence and IMT values displayed a notable difference between men and women, we carried out sex-specific analyses in addition to analyzing the overall data. Rs702553 at the PDE4D gene was selected because it conferred a risk for young stroke in our previous report. Previous young stroke data (190 cases and 211 controls) with an additional 532 control subjects without ultrasonic data were shown as a cross-validation for the genetic effect. RESULTS: In the overall analyses, the rare homozygote of rs702553 led to an OR of 3.1 (p = 0.034) for a plaque index > or = 4. When subjects were stratified by sex, the genetic effect was only evident in men but not in women. Comparing male subjects with plaque index > or = 4 and those with plaque index = 0, the TT genotype was over-represented (27.6% vs. 13.4%, p = 0.008). For dichotomized IMT data in men, the TT genotype had an OR of 2.1 (p = 0.032) for a thicker IMT at the common carotid artery compared with the (AA + AT) genotypes. In women, neither IMT nor plaque index was associated with rs702553. Similarly, SNP rs702553 was only significant in young stroke men (OR = 1.8, p = 0.025) but not in women (p = 0.27). CONCLUSIONS: The present study demonstrates a sex-differential effect of PDE4D on IMT, plaque index and stroke, which highlights its influence on various aspects of atherogenesis.

Dataset Information

Phosphodiesterase 4D single-nucleotide polymorphism 83 and cognitive dysfunction in carotid endarterectomy patients.

Publications

Phosphodiesterase 4D single-nucleotide polymorphism 83 and cognitive dysfunction in carotid endarterectomy patients.

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