Association Between Phosphodiesterase4D Gene Polymorphism And Carotid Atherosclerosis In Patients With Acute Atherosclerotic Cerebral Infarction

Background:Stroke is a malady afflicting worldwide human beings, especially for Chinese. In China, there are approximately7million stroke survivors, of which70%are ischemic stroke sufferers. More and more younger people have developed cerebral infarction in recent years with the changing of lifestyle. Statistics suggest that the incidence of stroke in young adults is up to3.4-11.3per one hundred thousand people. Obviously, stroke has taken a heavy toll on the society, economy or even people’s mentality. The main culprit for cerebral infarction is atherosclerosis(AS), and carotid and vertebral-basilar arteries are very vulnerable to brain AS. In fact, the majority of ischemic events are not caused by those thickest vessels, but by atherosclerotic plaque rupture and thrombosis in the proximal vessels. Thus, cerebral infarction is inextricably linked with carotid artery AS. One typical atherosclerotic plaque is comprised of lipid core and fibrous cap, while the vulnerable plaque, which has thinner fibrous cap, weaker resistance to mechanical force and is more easier to rupture, takes main responsibility for cerebral infarction attacking. Therefore, it is very significant for the prevention and cure of cerebral infarction to explore the specific association and mechanism between gene in patients with cerebral infarction and carotid artery AS.Phosphodiesterase(PDE), widely spreading in human bodies, mainly dwells in the inflammatory cells like mastocyte, macrophage, eosinophilic granulocyte, lymphocyte and epithelial cells and can be divided into PDE4A, PDE4B, PDE4C and PDE4D. As one member of PDE superfamily, PDE4D could selectively degrade Cyclic Adenosine monophosphate(cAMP), promote smooth muscle cells proliferation or accelerate their migration, which is the pathophysiologic mechanism between PDE4D and stroke. Gretarsdottir S has expounded the correlation of PDE4D gene with stroke from the perspective of single nucleotide polymorphism(SNP) and identified that multiple sites were associated with carotid atherosclerotic cerebral infarction. Song is the first person who found that rs918592site might be linked with African American women and the Caucasus stroke. He Y has reported the correlation between rs918592site and ischemic stroke in Chinese Han population in Henan, while the association of rs918592site with Chinese southern stroke patients has also been reported. However, currently, studies on the specific mechanism remain scarce.Objective:To investigate the association between PDE4D gene rs918592site polymorphism and the vulnerable plaque and carotid intima-media thickness(CIMT) in patients with acute atherosclerotic cerebral infarction. And, further, to shed light on the specific mechanism of PDE4D gene rs918592site polymorphism with carotid atherosclerosis in patients with acute atherosclerotic cerebral infarction. Methods:Between February2010and November2012,502patients with acute atherosclerotic cerebral infarction who ever were hospitalized in department of neurology, Taizhou hospital, Zhejiang Province were collected. Polymerase chain reaction-restriction enzyme fragment length polymorphism(PCR-RFLP) was adopted to analyze PDE4D gene rs918592site polymorphism of all patients. In a addition, ultrasound was used to measure carotid intima-media thickness(CIMT). According to classification criteria of carotid plaque by ultrasound, of399patients combined with carotid plaque,253patients with high plaque echogenicity were categorized as stable plaque group, the remaining146patients with mixed or low plaque echogenicity were labeled as vulnerable plaque group. Then, PDE4D gene rs918592site polymorphism difference between the two groups was compared. Also, CIMT difference among patients with varied genotypes was interpreted.Result:1. These risk factors, including smoking history [P=0.039, OR=1.753,95%CI (1.029-2.987)], low-density lipoprotein cholesterol level [P=0.000, OR=2.537,95%CI (1.599-4.024)], AA+AG genotype in PDE4D gene rs918592site [P=0.017, OR=2.037,95%CI (1.137-3.651)], were finally incorporated into the model of stable plaque group and vulnerable plaque group by non-conditional logistic regression analysis.2. There was significant difference in AA+AG genotype frequency between vulnerable plaque group and stable plaque group [87.0%vs75.5%, P=0.006, OR=2.170,95%CI(1.238-3.802)]. And There was also significant difference in A allele genotype frequency distribution between the two groups [61.3%vs53.4%, P=0.029, OR=1.385,95%CI(1.033-1.856)]. 3. Carotid intima-media thickness(CIMT) of GG genotype and AA+AG genotype were (1.17±0.20)mm and (1.19±0.18) mm, respectively (P>0.05).Conclusion:1. There was a correlation between PDE4D gene rs918592site polymorphism and carotid plaque stability in Han nationality patients with acute atherosclerotic cerebral infarction from Taizhou, Zhejiang Province, while the former had no association with carotid intima-media thickness(CIMT).2. AA+AG genotype in PDE4D gene rs918592site was one of potential risk factors contributing the formation of vulnerable plaque, And A allele might be a genetic susceptibility gene which leads to carotid plaque rupture.