Margaglione M, Cappucci G, Colaizzo D, Giuliani N, Vecchione G, Grandone E, Pennelli O, Di Minno G
Unita' di Aterosclerosi e Trombosi and Direzione Sanitaria, IRCCS Casa Sollievo della Sofferenza, S Giovanni Rotondo, Italy.
Arterioscler Thromb Vasc Biol. 1998 Feb;18(2):152-6. doi: 10.1161/01.atv.18.2.152.
A family history of ischemic events is a major determinant of coronary artery disease (CAD). Plasma levels of plasminogen activator inhibitor 1 (PAI-1) modulate this risk. A deletion/insertion polymorphism within the PAI-1 locus (4G/5G) affects the expression of this gene. We investigated the relationship between the PAI-1 4G/5G polymorphism in 1179 healthy employees of our institution and the occurrence of CAD in their first-degree relatives. A family history of documented ischemic coronary disease was assessed by a modified WHO questionnaire. The PAI-1 4G/5G polymorphism was evaluated by polymerase chain reaction and endonuclease digestion. The group with a first-degree relative who had suffered from a coronary ischemic episode had a higher number of homozygotes for the deleted allele (4G/4G) of the PAI-1 gene compared with subjects without such a family history (odds ratio [OR] = 1.62, 95% confidence interval [CI]=1.17 to 2.25; P=.005). The frequency of the 4G allele was abnormally high as well (OR=1.29, 95% CI=1.04 to 1.60; P=.025). The individuals with a positive family history were older (P<.001) and exhibited a higher body mass index (P=.033) and total cholesterol levels (P<.001) than those without. In a multiple logistic regression analysis, age (P=.006) and PAI-1 4G/4G (P=.024) independently contributed to a family history of coronary heart disease, with 4G/4G carriers exhibiting a more frequent family history of CAD (OR=1.60). The PAI-1 4G/5G polymorphism to some extent thus accounts for the risk of CAD related to a family history for such an event. These findings support the hypothesis that the 4G variant is a transmissible coronary risk factor.
缺血性事件家族史是冠状动脉疾病（CAD）的主要决定因素。纤溶酶原激活物抑制剂1（PAI - 1）的血浆水平可调节这种风险。PAI - 1基因座内的缺失/插入多态性（4G/5G）会影响该基因的表达。我们调查了本机构1179名健康员工的PAI - 1 4G/5G多态性与其一级亲属中CAD发生情况之间的关系。通过改良的WHO问卷评估有记录的缺血性冠心病家族史。通过聚合酶链反应和核酸内切酶消化评估PAI - 1 4G/5G多态性。与没有此类家族史的受试者相比，有一级亲属发生过冠状动脉缺血事件的组中，PAI - 1基因缺失等位基因（4G/4G）的纯合子数量更多（优势比[OR]=1.62，95%置信区间[CI]=1.17至2.25；P = 0.005）。4G等位基因的频率也异常高（OR = 1.29，95% CI = 1.04至1.60；P = 0.025）。有阳性家族史的个体比没有的个体年龄更大（P < 0.001），体重指数更高（P = 0.033），总胆固醇水平更高（P < 0.001）。在多因素逻辑回归分析中，年龄（P = 0.006）和PAI - 1 4G/4G（P = 0.024）独立地与冠心病家族史相关，4G/4G携带者的CAD家族史更常见（OR = 1.60）。因此，PAI - 1 4G/5G多态性在一定程度上解释了与此类事件家族史相关的CAD风险。这些发现支持了4G变异体是一种可遗传的冠状动脉危险因素这一假说。
