ACE2基因多态性与原发性高血压和颈动脉IMT相关性研究
摘要
目的：观察ACE2基因A9570G多态性在人群中的分布,超声测量高血压患者颈动脉内中膜厚度(IMT),并探讨两者的关系。
方法：选择符合入选标准的204例高血压患者和211例健康人群,所有受试者测量身高、体重、血压,测定空腹血糖、血脂、肝功能、肾功能。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法,进行ACE2基因分型。随访94名高血压患者,测量颈动脉内径和内中膜厚度。应用χ2检验比较组间基因型及等位基因频率,应用Logistic回归分析校正风险因素后,判别ACE2基因不同基因型与高血压及颈动脉IMT的关系。
1、在男性人群中,高血压组G基因型和A基因型频率分别为59%和41%,对照组为44%和56%,两组间基因型分布有统计学差异(χ2=4.907,P=0.027)。
2、在女性人群中,高血压组AA、AG、GG基因型分别占22%、37%和41%,对照组为22%、44%和34%,基因型分布无统计学差异(χ2=1.347,P=0.510)。高血压组A和G等位基因频率分别为41%和59%,对照组为44%和56%,两组间等位基因频率无统计学差异(χ2=0.644,P=0.422)。
3、运用Logistic回归分析对年龄、体重指数、腰臀比、胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、吸烟史、饮酒史、高血压家族史等混杂因素校正后,G等位基因仍是男性高血压发病的危险因素之一(P=0.042,OR=1.241,95%CI=1.036-1.673),而不是女性高血压发病的危险因素。
4、彩超检查结果显示,男性不同基因型高血压患者颈动脉IMT无差异(χ2=0.009,P=0.923)。女性不同基因型高血压患者颈动脉IMT亦无差异(χ2=0.131,P=0.718)。
1、ACE2基因A9570G多态性与男性高血压病相关,G等位基因可能是男性患高血压的易感基因。
2、ACE2基因A9570G多态性与女性高血压病不相关。
3、ACE2基因A9570G多态性与高血压患者颈动脉IMT厚度不相关。
Objective:To investigate the relationship of ACE2 gene polymorphism with EH susceptibility and IMT of carotid in Hunan Han population.
Methods:204 hypertension patients and 211 controls were recruited in this trail. Height, weight,blood pressure,fasting blood glucose, triglyceride,cholesterol,high density lipoprotein cholesterol,low density lipoprotein cholesterol,liver function and renal function were tested. The distribution of ACE2 gene A9570G polymorphism were analyzed by PCR-RFLP in all participants.The carotid arteries were performed with ultrsonography in 96 patients.χ2method was performed to evaluate association of genotype with essential hypertension. Logistic regression was performed to evaluate whether the different genotypes become the risk factor of essential hypertension and IMT.
1. In male, Genotype frequencies for ACE2 gene A9570G G and A genotypes were 59% and 41% in hypertension group respectively,44% and 56% in controls.There was significant difference of genotype distribution between the cases and controls (χ2=4.907, P=0.027)
2. In female, genotype frequencies for ACE2 gene A9570G AA,AG and GG genotypes were 22%,37% and 41% in hypertension group respectively,22%、44% and 34% in controls. There was no significant difference of genotype distribution between the cases and controls (χ2 =1.347, P=0.510).Allele frequencies of ACE2 gene has no significant difference between the cases and controls neither (χ2=0.644, P=0.422).
3.When adjusted by risk factors including age, BMI, WHR, FBG, triglyeride, cholesterol, high density lipoprotein and low density lipoprotein, smoking, taking alcohol, EH family hostory, using logistic regression method analysis founded that there was relationship between ACE2 A9570G polymorphism and EH male group (P=0.042) but not in female group.
4.The carotid artery IMT had no significant different bewteen different alleles frequence and gene types both in male and female patient(χ2=0.009,P=0.923 andχ2=0.131, P=0.718).
l.The ACE2 gene A9570G polymorphism is associated with hypertension in male.G alleles may be the susceptibility gene of hypertension in male.
2.The ACE2 gene A9570G polymorphism are not associated with hypertension among three genetypes in female.
3.The ACE2 gene A9570G polymorphism is not associated with the carotid artery IMT in different alleles frequence nor genetypes both in male and female.
方法：选择符合入选标准的204例高血压患者和211例健康人群,所有受试者测量身高、体重、血压,测定空腹血糖、血脂、肝功能、肾功能。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法,进行ACE2基因分型。随访94名高血压患者,测量颈动脉内径和内中膜厚度。应用χ2检验比较组间基因型及等位基因频率,应用Logistic回归分析校正风险因素后,判别ACE2基因不同基因型与高血压及颈动脉IMT的关系。
1、在男性人群中,高血压组G基因型和A基因型频率分别为59%和41%,对照组为44%和56%,两组间基因型分布有统计学差异(χ2=4.907,P=0.027)。
2、在女性人群中,高血压组AA、AG、GG基因型分别占22%、37%和41%,对照组为22%、44%和34%,基因型分布无统计学差异(χ2=1.347,P=0.510)。高血压组A和G等位基因频率分别为41%和59%,对照组为44%和56%,两组间等位基因频率无统计学差异(χ2=0.644,P=0.422)。
3、运用Logistic回归分析对年龄、体重指数、腰臀比、胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、吸烟史、饮酒史、高血压家族史等混杂因素校正后,G等位基因仍是男性高血压发病的危险因素之一(P=0.042,OR=1.241,95%CI=1.036-1.673),而不是女性高血压发病的危险因素。
4、彩超检查结果显示,男性不同基因型高血压患者颈动脉IMT无差异(χ2=0.009,P=0.923)。女性不同基因型高血压患者颈动脉IMT亦无差异(χ2=0.131,P=0.718)。
1、ACE2基因A9570G多态性与男性高血压病相关,G等位基因可能是男性患高血压的易感基因。
2、ACE2基因A9570G多态性与女性高血压病不相关。
3、ACE2基因A9570G多态性与高血压患者颈动脉IMT厚度不相关。
Objective:To investigate the relationship of ACE2 gene polymorphism with EH susceptibility and IMT of carotid in Hunan Han population.
Methods:204 hypertension patients and 211 controls were recruited in this trail. Height, weight,blood pressure,fasting blood glucose, triglyceride,cholesterol,high density lipoprotein cholesterol,low density lipoprotein cholesterol,liver function and renal function were tested. The distribution of ACE2 gene A9570G polymorphism were analyzed by PCR-RFLP in all participants.The carotid arteries were performed with ultrsonography in 96 patients.χ2method was performed to evaluate association of genotype with essential hypertension. Logistic regression was performed to evaluate whether the different genotypes become the risk factor of essential hypertension and IMT.
1. In male, Genotype frequencies for ACE2 gene A9570G G and A genotypes were 59% and 41% in hypertension group respectively,44% and 56% in controls.There was significant difference of genotype distribution between the cases and controls (χ2=4.907, P=0.027)
2. In female, genotype frequencies for ACE2 gene A9570G AA,AG and GG genotypes were 22%,37% and 41% in hypertension group respectively,22%、44% and 34% in controls. There was no significant difference of genotype distribution between the cases and controls (χ2 =1.347, P=0.510).Allele frequencies of ACE2 gene has no significant difference between the cases and controls neither (χ2=0.644, P=0.422).
3.When adjusted by risk factors including age, BMI, WHR, FBG, triglyeride, cholesterol, high density lipoprotein and low density lipoprotein, smoking, taking alcohol, EH family hostory, using logistic regression method analysis founded that there was relationship between ACE2 A9570G polymorphism and EH male group (P=0.042) but not in female group.
4.The carotid artery IMT had no significant different bewteen different alleles frequence and gene types both in male and female patient(χ2=0.009,P=0.923 andχ2=0.131, P=0.718).
l.The ACE2 gene A9570G polymorphism is associated with hypertension in male.G alleles may be the susceptibility gene of hypertension in male.
2.The ACE2 gene A9570G polymorphism are not associated with hypertension among three genetypes in female.
3.The ACE2 gene A9570G polymorphism is not associated with the carotid artery IMT in different alleles frequence nor genetypes both in male and female.
引文
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[29]Langeveld BE, Henning RH, de Smet BJ, et al., Rescue of arterial function by angiotensin-(1-7):towards improvement of endothelial function by drug-eluting stents, Neth Heart J, vol.16,291-292,2008. 发现ACE2蛋白产物及受体。ACE2对调节肾内AngⅡ的浓度也起到重要作用,在大多数实验中,ACE2可以拮抗肾内AngⅡ浓度增加引起的血压升高。Crackower MA报道肾脏ACE2表达与高血压呈负相关。盐敏感高血压大鼠肾脏局部ACE2 mRNA水平较血压正常大鼠低,在给予高盐饮食后,其肾脏内ACE2mRNA水平进一步下降。相对于血压正常大鼠,自发高血压大鼠和易卒中高血压大鼠肾脏内ACE2蛋白含量均降低。糖尿病肾病大鼠肾内ACE2蛋白合成减少,拮抗AngⅡ减弱，其肾脏纤维化严重程度与ACE2基因多态性相关。还有研究发现,Ang1-7可使入球动脉舒张。予正常血压的大鼠或狗注入Ang1-7后,可起利尿效果。在离体近端肾小管培养液中加入AngⅠ后,在AngⅡ浓度升高的同时,Ang1-7、Ang1-9含量也随之升高,使用ACE2阻滞剂DX600可阻断该代偿反应的发生。 在肾移植患者及糖尿病肾病患者早期肾小球和肾小管中,内皮细胞分泌ACE2增多,而晚期含量却降低,使用ACEI可延缓该现象的出现,提示ACE2可以发挥肾脏保护作用。但也有不同的研究结论。给水负荷大鼠静脉注射Angl-7发挥抗利尿作用,并引起钠重吸收增加。Arima发现,肾脏局部Ang1-7不能发挥舒张肾脏血管或拮抗局部AngⅡ的作用。
综上所述,RAS系统的各部分的平衡紊乱在高血压的发生、发展和靶器官损害方面起着重要作用。ACE2可对抗AngⅡ生物学活性,发挥舒张血管、抗增殖、保护心脏功能等作用。对ACE2基因多态性的研究显示ACE2基因多态性在人类高血压的发病中起重要作用,ACE2基因可能是高血压发病的候选基因。与其相关的研究对防止高血压及其他心血管疾病有重要意义。
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[29]Langeveld BE, Henning RH, de Smet BJ, et al., Rescue of arterial function by angiotensin-(1-7):towards improvement of endothelial function by drug-eluting stents, Neth Heart J, vol.16,291-292,2008. 发现ACE2蛋白产物及受体。ACE2对调节肾内AngⅡ的浓度也起到重要作用,在大多数实验中,ACE2可以拮抗肾内AngⅡ浓度增加引起的血压升高。Crackower MA报道肾脏ACE2表达与高血压呈负相关。盐敏感高血压大鼠肾脏局部ACE2 mRNA水平较血压正常大鼠低,在给予高盐饮食后,其肾脏内ACE2mRNA水平进一步下降。相对于血压正常大鼠,自发高血压大鼠和易卒中高血压大鼠肾脏内ACE2蛋白含量均降低。糖尿病肾病大鼠肾内ACE2蛋白合成减少,拮抗AngⅡ减弱，其肾脏纤维化严重程度与ACE2基因多态性相关。还有研究发现,Ang1-7可使入球动脉舒张。予正常血压的大鼠或狗注入Ang1-7后,可起利尿效果。在离体近端肾小管培养液中加入AngⅠ后,在AngⅡ浓度升高的同时,Ang1-7、Ang1-9含量也随之升高,使用ACE2阻滞剂DX600可阻断该代偿反应的发生。 在肾移植患者及糖尿病肾病患者早期肾小球和肾小管中,内皮细胞分泌ACE2增多,而晚期含量却降低,使用ACEI可延缓该现象的出现,提示ACE2可以发挥肾脏保护作用。但也有不同的研究结论。给水负荷大鼠静脉注射Angl-7发挥抗利尿作用,并引起钠重吸收增加。Arima发现,肾脏局部Ang1-7不能发挥舒张肾脏血管或拮抗局部AngⅡ的作用。
综上所述,RAS系统的各部分的平衡紊乱在高血压的发生、发展和靶器官损害方面起着重要作用。ACE2可对抗AngⅡ生物学活性,发挥舒张血管、抗增殖、保护心脏功能等作用。对ACE2基因多态性的研究显示ACE2基因多态性在人类高血压的发病中起重要作用,ACE2基因可能是高血压发病的候选基因。与其相关的研究对防止高血压及其他心血管疾病有重要意义。
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