背景:基质金属蛋白酶10(MMP-10)与颈动脉粥样硬化(CAS)和脑梗死密切相关。MMP-10rs17435959多态性在MMP-10基因外显子1的密码子4处引起亮氨酸到缬氨酸的转换,并且可能具有功能作用。
目的:探讨MMP-10rs17435959多态性与CAS斑块形成及稳定性的关系。
方法:本病例对照研究包含738名首次来到我们健康体检中心的访客。根据颈动脉超声检查,访客分为易损斑块组(41-86岁,141男,105女性),稳定斑块组(41-86岁,141男,105名女性)和无斑块组(41-85岁,141男,105名女性)。三组中的所有访客都是性别和年龄匹配的,没有心血管和脑血管疾病。通过实时聚合酶链反应限制对多态性进行基因分型。
结果:与GG基因型相比,CC和CG基因型的频率在易损斑块组中明显高于无斑块组(18.7%vs.7.7%,未调整P=0.002)。此外,与G等位基因相比,易损斑块组的C等位基因频率明显高于无斑块组(10.4%vs.3.9%,未调整P=0.000),易损斑块组高于稳定斑块组(10.4%vs.5.1%,未调整P=0.008)。二元logistic回归分析显示CC和CG基因型是CAS斑块形成的独立危险因素(P=0.019,OR=1.961,95%CI[1.117,3.444])和易损性(P=0.035,OR=1.842,95%CI[1.045,3.247])。此外,具有C等位基因的个体显示出更高水平的纤维蛋白原,是CAS斑块形成的独立危险因素(P=0.000,OR=2.425,95%CI[1.475,3.985])。
结论:rs17435959多态性与CAS斑块的形成和易损性相关。具有变异型MMP-10的个体显示出更高水平的纤维蛋白原,促进了CAS斑块的形成。
BACKGROUND: Matrix metalloproteinase 10 (MMP-10) has a close relationship with carotid atherosclerosis (CAS) and cerebral infarction. The MMP-10 rs17435959 polymorphism causes a leucine to valine transition at codon 4 in exon 1 of the MMP-10 gene and may have functional effects.
OBJECTIVE: To investigate the relationship between the MMP-10 rs17435959 polymorphism and the formation and stability of CAS plaques.
METHODS: The present
case-control study contains 738 visitors who came to our health examination center for the first time. According to the carotid ultrasound examinations, visitors were classified into the vulnerable plaque group (41-86 years old, 141 male, 105 female), the stable plaque group (41-86 years old, 141 male, 105 female) and the no plaque group (41-85 years old, 141 male, 105 female). All visitors in the three groups were sex- and- age-matched, and cardiovascular and cerebrovascular diseases were absent. The polymorphism was genotyped by real-time polymerase chain reaction- restriction.
RESULTS: Compared to the GG genotype, the frequency of the CC and CG genotypes was significantly more common in the vulnerable plaque group than in the no plaque group (18.7% vs. 7.7%, unadjusted P = 0.002). Moreover, compared to the G allele, the frequency of the C allele was significantly more common in the vulnerable plaque group than in the no plaque group (10.4% vs. 3.9%, unadjusted P = 0.000) and in the vulnerable plaque group than in the stable plaque group (10.4% vs. 5.1%, unadjusted P = 0.008). Binary logistic regression showed that the CC and CG genotype was independent risk factor for the formation (P = 0.019, OR = 1.961, 95% CI [1.117, 3.444]) and vulnerability (P = 0.035, OR = 1.842, 95% CI [1.045, 3.247]) of CAS plaques. Moreover, individuals who have the C allele showed a higher level of fibrinogen, which was an independent risk factor for the formation of CAS plaques (P = 0.000, OR = 2.425, 95% CI [1.475, 3.985]).
CONCLUSIONS: The rs17435959 polymorphism was associated with the formation and vulnerability of CAS plaques. Individuals who had variant-type MMP-10 showed higher levels of fibrinogen, which promoted the formation of CAS plaques.