| Abstract: | Apolipoprotein E 是一種由299個胺基酸所構成的蛋白質，存在於乳糜小體(chylomicron)，極低密度脂蛋白(VLDL)，低密度之蛋白(LDL)和高密度脂蛋白(HDL)中，其主要的功能在調節脂質的代謝及運送。在人類中，製造Apo E 脂蛋白的基因據多型性的特性(polymorphism)。之前的研究顯示，Apo E4 基因型的人對動脈硬化及心血管疾病有促進作用，而Apo E2 基因型的人則對於動脈硬化及心血管疾病有保護作用。但在文獻探討後，我們發現目前的研究報告絕大多數是都是針對已發病的族群為研究對象，卻少有針對中年健康族群的，本研究即是針對健康的中年族群，探討脂蛋白 E 基因的多型性對頸動脈內膜厚度(Intima-media-Thickness, IMT)、斑塊指數(Plague index)、阻力指數(resistance index)及血流速度(flow velocity) 的影響。
材料與方法：總共有103為健康的中年人參與此次研究。具有高血壓、高血脂、糖尿病、腎功能異常及心血管疾病症狀的人皆排除在此研究對象外。所有參與者皆經過詳細的身體檢查及評估，抽血收集血清及血球，利用polymer chain reaction (PCR) ，酵素切割及電泳法以進行脂蛋白 E 基因型的判定，使用B-mode 超音波以求出IMT, Plague Index, Resistance Index 及 flow velocity。
結果：E2,E3,E4 的基因行的比例分別為17.4% , 72.8%, 9.7%。我們發現血中總脂質、頸動脈內膜厚度及最大頸動脈內膜厚度隨著E2到E4的基因型有顯著的增加。經控制年齡、BMI、抽煙指數及性別等干擾因子之後，ApoE4 基因行在IMT(0.795±0.052mm)及IMTmax(1.327±0.173mm) 這兩項數據均較ApoE3基因型的這組高(IMT=0.635±0.019mm, IMTmax = 0.720±0.620mm)(P=0.005 in IMT, P=0.01 in IMTmax)。至於ApoE2 和 ApoE3 基因型，則沒有統計學上的意義。
結論：我們的資料顯示在中年健康的族群中，ApoE4 基因型和ApoE3基因型相比有較高的血漿脂質濃度及對頸動脈早期硬化具有較強之誘發作用。
Apolipoprotein E is a 299-amino acid protein found in chylomicron, VLDL, IDL and HDL; and it is a major regulator of lipid metabolism. In Human, the apolopoprotein E gene is polymorphic. Clinical and autoptical studies have suggested a predisposing role for E4 genotype and a protective role for E2 genotype in the development of atherosclerosis and cardiovascular disease. But few data are available on the role of apo E genotype in early asymptomatic carotid atherosclerosis. Ultrasound assessment of the arterial wall allowed in vivo study of atherosclerosis even in its early stages. This study is designed to investigate the association between polymorphism of apoE gene and carotid intima-media thickness (IMT), plaque index, resistance index and flow velocity as assessed by ultrasound in a group of middle-aged asymptomatic.
Material and Method:103 healthy subjects who were nondiabetic, nonhypertensive and asymptomatic for cardiovascular disease were invited to participate in this study. Blood samples were obtained after an overnight fasting. Cholesterol and triglycerides was analyzed enzymatically. ApoE genotype were determined from amplified apoE sequence by restriction isotyping. B-mode ultrasound was used to quantify the maximum IMT, mean IMT a 4 sited on the far wall below 1cm and 2 cm to carotid bifurcation.
Result: The frequencies of E2, E3 and E4 alleles in our study were 0.18, 0.78 and 0.09 respectively. As expected subjects with E4 allele had the highest levels of total serum lipid, subjects with E2 allele has the lowest levels and those with E3 allele genotype had intermediate levels. The echographic measurements of carotid IMT showed increased values from E2 to E4 carries(p=0.01). After adjustment of for total serum lipid level, age, sex and body mass index, ANOVA showed that the common carotid IMT and IMTmax was significantly greater in subjects with E4 allele as compared with E3.
Conclusion: Our data confirm the influence of apoE4 on serum lipid levels and may induced the early atherosclerosis of carotid arteries in middle-aged healthy subjects. More information is needed to confirm the results. |
