Manfredi Samantha, Masetti Serena, Botto Nicoletta, Colombo Maria Giovanna, Terrazzi Marco, Vassalle Cristina, Biagini Andrea, Andreassi Maria Grazia
Laboratory of Cellular Biology, CNR Institute of Clinical Physiology, G. Pasquinucci Hospital, Massa, Italy.
Environ Mol Mutagen. 2002;40(2):110-5. doi: 10.1002/em.10098.
A common polymorphism at codon 72 (Arg72Pro) of the p53 gene, a gene which codes for a tumor-suppressor protein with both antiproliferative and pro-apoptotic actions, has recently been reported to be a risk factor for coronary luminal narrowing after angioplasty. However, the association of the polymorphism with coronary artery disease (CAD) risk has not been studied. We evaluated the distribution of the Arg72Pro genotype in 250 patients, 180 with angiographically documented CAD and 70 with normal coronary angiography, by using polymerase chain reaction amplification of patient DNA followed by restriction enzyme digestion. We also examined the association between the Arg72Pro genotype and chromosome damage in 82 male patients (60 CAD and 22 no-CAD) by the micronucleus (MN) test in human lymphocytes, a sensitive assay for chromosome breakage and aneuploidy. The frequencies of Pro/Pro, Pro/Arg, and Arg/Arg genotypes in CAD patients were not significantly different from those who were CAD-free (chi(2) = 0.20, P = 0.90) and not significantly associated with the extent and severity of CAD. A significant increase in MN frequency was observed in relation to smoking status (8.4 +/- 0.6, 11.9 +/- 1 and 12.0 +/- 1.6, for non smokers, ex-smokers and smokers, respectively; P = 0.02). Moreover, diabetic patients showed higher levels of MN than normal patients (13.5 +/- 1.4 vs. 9.6 +/- 0.5, P = 0.0025). Also, MN frequency was significantly higher in CAD patients than in no-CAD patients (11.2 +/- 0.7 vs. 8.0 +/- 0.9, P = 0.02) and increased with the number of affected vessels (9.3 +/- 0.1, 12.2 +/- 1.5 and 12.5 +/- 1.3 for one-, two-, and three-vessel disease, respectively; P = 0.02). However, there were no associations between MN frequency and the Arg72Pro polymorphism. Although there appears to be an association between CAD and MN frequency, our results indicate that the Arg72Pro polymorphism does not have a significant impact on CAD or MN frequencies.
p53基因第72位密码子（Arg72Pro）存在一种常见的多态性，该基因编码一种具有抗增殖和促凋亡作用的肿瘤抑制蛋白，最近有报道称其是血管成形术后冠状动脉管腔狭窄的一个危险因素。然而，尚未研究这种多态性与冠状动脉疾病（CAD）风险之间的关联。我们通过对患者DNA进行聚合酶链反应扩增，然后进行限制性酶切消化，评估了250例患者中Arg72Pro基因型的分布情况，其中180例患者经血管造影证实患有CAD，70例患者冠状动脉造影正常。我们还通过人淋巴细胞微核（MN）试验，对82例男性患者（60例CAD患者和22例无CAD患者）中Arg72Pro基因型与染色体损伤之间的关联进行了研究，MN试验是一种检测染色体断裂和非整倍体的敏感方法。CAD患者中Pro/Pro、Pro/Arg和Arg/Arg基因型的频率与无CAD患者相比无显著差异（χ² = 0.20，P = 0.90），且与CAD的范围和严重程度无显著关联。观察到MN频率与吸烟状况显著相关（非吸烟者、已戒烟者和吸烟者的MN频率分别为8.4±0.6、11.9±1和12.0±1.6；P = 0.02）。此外，糖尿病患者的MN水平高于正常患者（13.5±1.4对9.6±0.5，P = 0.0025）。而且，CAD患者的MN频率显著高于无CAD患者（11.2±0.7对8.0±0.9，P = 0.02），并且随着受累血管数量的增加而升高（单支血管病变、双支血管病变和三支血管病变患者的MN频率分别为9.3±0.1、12.2±1.5和12.5±1.3；P = 0.02）。然而，MN频率与Arg72Pro多态性之间无关联。尽管CAD与MN频率之间似乎存在关联，但我们的结果表明，Arg72Pro多态性对CAD或MN频率没有显著影响。
