| Objective: Ischemic stroke is the most common disease in the elderly population and become one of the main causes of death in many countries. Intracranial atherosclerotic stenosis or occlusion is a well-recognized cause of ischemic stroke in Chinese. Therefore, it's important to find out risk factors of intracranial atherosclerosis and give an intervention for prevention of stroke. Serum paraoxonase-1 (PON-1) is a high-density lipoprotein-bound enzyme which can prevent oxidation of low-denisty lipoprotein by hydrolyzing lipid peroxides and thus exert an anti-atherogenic effect. PON-1 shows two common polymorphisms, Gln→Arg governed by two common alleles named Q and R; Met→Leu governed by two common alleles named M and L. PON-1 gene polymorphisms have been proposed as genetic markers of risk for cardiovascular disease. The aim of this study is to explore the relation between the Q192R or M55L polymorphism of paraoxonase-1 and acute ischemic stroke with intracranial atherosclerosis stenosis and to investigate the risk factors of intracranial atherosclerosis stenosis. Methods: We conducted a case-control study. 53 acute ischemic stroke with intracranial atherosclerosis stenosis were enrolled this study, whose age range from 44 to 76 years. A total of 55 age-and gender-matched health individuals without intracranial atherosclerosis stenosis were enrolled as control. All studied population were the Han nationality living in shijiazhuang city, China. Intracranial atherosclerosis stenosis or occlusion was diagnosed with TCD and MRA. Diagnosis standard of intracranial artery stenosis by TCD : the systolic velocity of intracranial artery was greater than 140 cm/s, accompanied with turbulence and murmur. In this study, all patients with extracranial carotid stenosis or occlusion were excluded. A standard questionnaire was administered to obtain information of disease history for all participants, including hypertension, hyperlipidemia, diabetes mellitus, smoking and so on. Height and weight were measured after each subject removed shoes and outer wear; height was measured to the nearest 1 mm on a portable stadiometer, and weight was measured to the nearest 0.1 Kg with the subject standing motionless on the scale. BMI was calculated as weight (Kg)/height2 (m2). Cigarette smoking was defined as those who smoked at least one cigarette per day and had smoked more than 1 year. Hypertension was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg, or treatment with antihypertensive medication. Diabetes mellitus was defined as fasting blood glucose levels above 110 mg/dl, or treatment with antidiabetic medication.Hyperlipidemia was defined as total cholesterol >5.1 m mol/L and/or low-density lipoprotein (LDL)>3.1 m mol/L or currently taking lipid lowing medications. Peripheral venous blood samples were drawn from all subjects after overnight fasting to analyze the lipid profile and the blood glucose levels and to extract genomic DNA. The genotype and allele frequency of PON-1 192Q/R and 55M/L polymorphism was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all subjects. Variables, including age, sex, BMI, smoking, blood pressure, blood glucose, blood lipid, history of hypertension, history of hyperlipidemia, history of diabetes mellitus, history of family of vascular disease and paraoxonase-1 Q192R and M55L genotype, were analyzed by multivariate logistic regression to determine the independent risk factors for intracranial atherosclerosis stenosis. Results: The frequencies of Q (Gln) and R (Arg) alleles for the PON-1 Q192R polymorphism were 0.23 and 0.77 respectively in study group, which were 0.38 and 0.62 in control group. Genotype frequencies were concordant with Hardy-Weinberg equilibrium both study group and control group. The most common genotype of PON-1 Q192R gene polymorphism was RR genotype, the next one was QR genotype and the lowest was QQ genotype in this study. The study group showed a lower frequency of QQ genotype, a higher frequency of RR and R allele as compared with thecontrol group. No differences were found in PON-1 gene QQ,QR and RR genotype between the two groups , but there was significant differences in R allele frequency between study group and control group(p<0.05). Our study demonstrated that R allele was a main determinant of intracranial atherosclerosis stenosis through multivariate logistic regression analysis (OR 1.51 95% CI 1.13-2.03). In type 2 diabetic patients the PON-1 192 R allele carriers displayed the increased risk of intracranial atherosclerosis stenosis compared with QQ genotype individuals (OR 1.90 95% CI 1.29-2.80). In smokers, the PON-1 192 R allele carriers had an odds ratio of 1.63 (95% CI 1.17-2.27) for intracranial atherosclerosis stenosis compared with QQ genotype individuals. The frequency of the paraoxonase M55L genotype and L allele didn't show significant difference between two groups. The frequency of L allele was only 0.019, and was less than that of the west population. Conclusions: Our data indicate that the PON-1 Q192R polymorphism is associated with intracranial atherosclerosis stenosis, R allele is a risk factor for intracranial atherosclerosis stenosis in HeBei Han nationality. There is an interaction between R allele gene and smoking or diabetes for the increased risk of intracranial atherosclerosis stenosis. The pathogenesis may be explained by a reduced ability of R allele to protect lipoproteins against peroxidation. But PON-1 M55L polymorphism is not associated with intracranial... |
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