| Background and Aims:Ischemic cerebrovascular disease(ICVD)is a polygenic inheritable disease caused mainly by the interaction of genetic and environmental factors. ICVD has been putting great burden on individuals, families and society because of its extremely complicated pathogenesis and extraordinarily high morbidity, deformity and mortality. China is one of the countries with high morbidity of ICVD and its incident rate is becoming increasingly high. Although the known danger factors like hypertension, diabetes, hyperlipemia, atherosclerosis, arrhythmia as well as smoking have been well controlled, many patients still inevitably suffer from ICVD, which arouses researchers'focus on finding out new danger factors of ICVD, especially determining the susceptibility of ICVD to different individuals from gene level.In 2003, Gretarsdott et al. found phosphodiesterase 4D (PDE4D) associated with familial inherited ICVD was related to the progression of atherosclerosis. PDE4D is specific to hydrolyze cyclic adenosine monophosphat(cAMP) whose existing level affects the proliferation and migration of angiocellulars. Thus PDE4D is able to control the existing level of cAMP through its existing level and activity and further to affect the process of atherosclerosis. Therefore, PDE4D has certain effect on the invasion risk of ICVD. PDE4D gene is different from the genes associated with the invasion risk of ICVD such as diabetes, abnormal metabolism of blood lipid and hypertension due to its independent effect on the pathogenesis of ICVD. Thus PDE4D gene is so far considered as the only canditate gene associated with stroke newly discovered. Therefore PDE4D gene has been arousing the interest of researchers around the world, but the research results are not so identical.PDE4D is firstly considered as the candidate gene of ICVD universally. To further investigate the relationship between PDE4D gene polymorphism and ICVD, polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP) was adopted to detect the polymorphism of PDE4D rs918592 and PDE4D rs2910829 in han population of Henan. The distribution of rs918592 and rsRS2910829 and the relationship between ICVD and rs918592 as well as rs2910829 were investigated to provide theory evidence for the prevention of ICVD.Study population:1 Patients 400 cases as patient group with ischemic cerebrovascular disease in departments of neurology in Henan province hospitals were enrolled from December 2007 to 2010.There were 238male and 162 female with an average of 51.15.±10.16 years. All of them are Han population.2 Controls 400unrelated heathy controls were selected from subjects in outpatient department who underwent regular check-up examination.235 of them were male and 165 were female with an averageof 46.00±12.04years.The cases of control group had no history of CHD, EH and DM.All of them are Han population.Methods:5ml EDTA-anticoagulated Peripheral blood were obtained from ICVD patients and control. Genomic DNA was extracted by phenol-chloroform extraction method and its content was determined by ultraviolet spectrophotometer.Using the primers, we performed polymerase chain reaction(PCR) amplification and refined frequence length polymorphism(RFLP).These products were electrophoresed on 2.5% agarose gels, and DNA was visualized by ethidium bromide straining. Statistical analysis:The frequence of the alleles and genotypes were counted and compared by the Chi-square test. Hardy-weinberg equilibrium was confirmed with the X2 test. Odds Rations(OR) and 95% confidence intervals(95%C1) were used to estimate the risk association to the genotype. All statistical procedures were performed with SPSS13.0 software package. P value<0.05 was taken as statistical significant.Results:1. The genotype distribution of the PDE4D rs918592 and rs2910829 polymorphism was compatible with the Hardy-Weinberg equilibrium in the ICVD group and control group.2. The frequency of the PDE4D rs918592 between ICVD group and control group exist strong difference, further,in accordance with the sex classification analysis, there was also significant difference in the genotype or allele frequency in male.3. In accordance with the age classification analysis, there was significant difference in the genotype or allele frequency of PDE4D rs2910829 in less than 45 years of age.4. The AA genotype of rs918592 is assoeiated with ICVD in an additive mode (P<0.05),rs918592 in dominant or recessive mode(P<0.05).5. The linkage analysis showed that:G-T and A-T haplotypes between cases and controls exist significant differences.6. The frequencies of PDE4D rs918592 and rs2910829 might exist difference in ethnic groups.Conclusion:1. Relative risk analysis showed that it carrying PDE4D rs918592 A allele may increase the risk of ischemic cerebrovascular disease, especially in male patients.2. Relative risk analysis showed that it may increase the risk of less than 45 years of age ischemic cerebrovascular disease carrying PDE4D rs2910829T allele.3. It suggestde that PDE4D G-T and A-T haplotypes are risk factors for Henan Han population. |
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