Ghilardi Giorgio, Biondi Maria Luisa, DeMonti Marco, Turri Olivia, Guagnellini Emma, Scorza Roberto
Dipartimento di Medicina, Chirurgia, e Odontoiatria, Clinica Chirurgica Generale, Università degli Studi di Milano-Polo S. Paolo, Milan, Italy.
Stroke. 2002 Oct;33(10):2408-12. doi: 10.1161/01.str.0000031929.05665.da.
The matrix metalloproteinases (MMPs) are a family of enzymes that are important in the resorption of extracellular matrix and are involved in atherogenesis. Recently, 2 common polymorphisms on MMP-1 (1G/2G) and MMP-3 (5A/6A) gene promoters have been described. The aim of this study was to investigate a possible association between MMP polymorphisms and increased risk of internal carotid artery (ICA) stenosis.
We studied 91 patients consecutively recruited for ICA stenosis who had undergone carotid endarterectomy and 133 subjects without ICA stenosis (controls). Polymorphic genotypes were determined by polymerase chain reaction and sequencing analysis.
The frequency of the 6A allele was significantly different between cases and controls: 0.62 and 0.50, respectively (odds ratio [OR], 1.58; 95% CI, 1.08 to 2.33; P=0.017). The frequency of 6A/6A genotype was significantly higher in cases with involvement of both carotids (OR, 3.13; 95% CI, 1.14 to 8.5; P=0.026) and in patients with stenosis >70% (OR, 2.55; 95% CI, 1.07 to 6.07; P=0.033). No significant differences were observed in MMP-1 distribution. Patients who were homozygous for both the 6A and 2G alleles had an elevated relative risk of ICA stenosis (OR, 2.66; 95% CI, 1.23 to 5.72; P=0.016). Multiple logistic regression analysis using the common risk factors and the 6A and 2G allele variants revealed that the 6A allele was an independent risk factor for ICA stenosis (P=0.049). When 6A/6A and 2G/2G were combined, the risk factor for ICA stenosis was 3-fold higher (OR, 3.31; 95% CI, 1.48 to 7.42; P=0.004).
Homozygosity for the 6A allele of the MMP-3 promoter is associated with carotid stenosis and, in association with MMP-1 2G homozygosity, predicts an increased risk of ICA stenosis. Even if obtained from a relatively limited patient series, these results might have relevant implications for treatment of ICA stenosis and possibly prevention of carotid-related stroke.
基质金属蛋白酶（MMPs）是一族在细胞外基质吸收中起重要作用且参与动脉粥样硬化形成的酶。最近，已报道了MMP-1（1G/2G）和MMP-3（5A/6A）基因启动子上的2种常见多态性。本研究的目的是调查MMP多态性与颈内动脉（ICA）狭窄风险增加之间的可能关联。
我们研究了91例因ICA狭窄而连续入选并接受颈动脉内膜切除术的患者以及133例无ICA狭窄的受试者（对照组）。通过聚合酶链反应和测序分析确定多态基因型。
病例组和对照组中6A等位基因的频率有显著差异：分别为0.62和0.50（优势比[OR]，1.58；95%可信区间[CI]，1.08至2.33；P = 0.017）。双侧颈动脉受累的病例中6A/6A基因型的频率显著更高（OR，3.13；95%CI，1.14至8.5；P = 0.026），狭窄>70%的患者中也是如此（OR，2.55；95%CI，1.07至6.07；P = 0.033）。在MMP-1分布方面未观察到显著差异。6A和2G等位基因均为纯合子的患者ICA狭窄的相对风险升高（OR，2.66；95%CI，1.23至5.72；P = 0.016）。使用常见风险因素以及6A和2G等位基因变异进行的多因素逻辑回归分析显示，6A等位基因是ICA狭窄的独立风险因素（P = 0.049）。当6A/6A和2G/2G合并时，ICA狭窄的风险因素高出3倍（OR，3.31；95%CI，1.48至7.42；P = 0.004）。
MMP-3启动子6A等位基因的纯合性与颈动脉狭窄相关，并且与MMP-1 2G纯合性相关时，预示着ICA狭窄风险增加。即使这些结果来自相对有限的患者系列，它们可能对ICA狭窄的治疗以及可能预防颈动脉相关卒中具有重要意义。
