广东汉族原发性高血压患者ACE基因多态性与ACE、PAI-1活性的相关性

Association of angiotensin I-converting enzyme gene polymorphism with ACE and PAI-1 levels in Guangdong Chinese Han patients with essential hypertension

目的研究广东汉族原发性高血压患者血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与ACE、纤溶酶原激活剂抑制物-1(PAI-1)活性的相关性。方法应用PCR方法扩增115例广东汉族人群原发性高血压患者及96例健康体检者ACE基因特异性片段,同时应用比色法测定血清ACE活性,发色底物法测定PAI-1活性,并对结果进行相关性分析。结果(1)高血压组ACEDD基因型频率(34.7%)和D等位基因频率(60.0%)显著高于对照组(15.6%和42.1%)(P均<0.05)。(2)高血压组血清ACE(217.18±57.35U/L)及血浆PAI-1活性(0.87±0.16U/ml)均显著高于对照组(169.13±47.64U/L,0.62±0.18U/ml)(P均<0.01);高血压组与对照组ACE与PAI-1活性均呈显著正相关(r分别为0.7913、0.7806,P均<0.01)。(3)高血压组DD基因型血清ACE(257.46±54.73U/L)、血浆PAI-1活性(0.97±0.16U/ml)显著高于ID基因型(213.28±51.36U/L,0.83±0.17U/ml)及II基因型(177.63±51.45U/L,0.72±0.15U/ml)(P均<0.01);ID基因型血清ACE、血浆PAI-1活性亦显著高于II型(P均<0.05)。结论(1)DD基因型以及D对位基因可能与广东汉族人群原发性高血压有关;(2)高血压患者血清ACE和血浆PAI-1活性增加,由ACE基因型所决定的ACE活性,可能参与血浆PAI-1水平的调节;(3)高血压患者纤溶受损可能存在一定的遗传背景,ACE基因DD型可能是高血压纤溶紊乱的危险因素。

Objective To investigate the association between angiotensin I-converting enzyme （ACE） gene and the levels of ACE and PAI-1 in Chinese Han patients with essential hypertension （EH） in Guangdong Province, Methods：Polymerase chain reaction was used to examine the ACE genotype, colorimetry used to measure the serum ACE level, and spectrophotometric assay performed to examine the plasma PAI-1 level in 115 EH patients and 96 healthy controls in Guangdong Province. Results The ACE DD genotype and D allele frequencies were significantly higher in EH group than in the control group （P〈 0.05）, and the EH patients also had significantly higher serum ACE level and plasma PAI-1 level than the control subjects （P〈 0.01）. The serum ACE level was positively correlated with plasma PAI-1 level in both EH group and control group （r=0.7913 and 0.7806, respectively, P〈0.01）. In EH group, the patients with DD genotype showed significantly higher serum ACE and plasma PAI-1 levels than those with ID and Ⅱ genotypes （P〈0.01）, and patients with ID genotype had significantly higher ACE and PAI-1 levels than those with Ⅱ genotype （P〈0.05）. Conclusion The DD genotype and D allele of ACE gene can be risk factors for essential hypertension in Chinese Han subjects in Guangdong Province, and the EH patients have elevated serum ACE and plasma PAI-1 levels. Increased ACE level due to DD polymorphism may play an important role in elevating plasma PAI-1 level. The genetic variation of ACE contributes to the balance of fibrinolytic pathway, which may be one of the pathological mechanisms linking the ACE I/D genotype and EH.