基质金属蛋白酶基因多态性与原发性高血压伴颈动脉粥样病变相关性研究

Association between polymorphisms of matrix metalloproteinases and essential hypertension complicated with carotid atherosclerosis

目的:探讨基质金属蛋白酶(matrix metalloproteinase,MMP)与原发性高血压(essential hypertension,EH)伴颈动脉粥样硬化(carotid atherosclerosis,CAS)的关系。方法:EH患者488例,汉族276例,维族212例,采用聚合酶链反应-限制性片断长度多态性技术测定MMPs基因多态性,依据是否存在颈动脉粥样病变分为CAS组293例和颈动脉内膜正常组(NS组)195例。检测各组血压、血脂水平,分别比较各组基因型频率及不同基因型发生EH的风险,分析EH伴CAS的可能危险因素。结果:(1)MMP-2TT基因型、T等位基因频率和MMP-36A/6A基因型、6A等位基因频率在CAS组高于NS组,差异有统计学意义(P<0.05)。(2)汉族MMP-2-735CT+TT和MMP-3-11716A/6A联合基因型优势比增加;维族MMP-2-735CT+TT和MMP-3-11716A/6A联合基因型优势比降低。(3)回归分析显示MMP-2C-735T基因型是维、汉族EH伴CAS的独立危险因素,MMP-3-11715A/6A基因型是汉族EH伴CAS的独立危险因素(P<0.05),与MMP-2具协同效应。结论:MMP-2和MMP-3在人群中的分布存在民族差异;MMP-2-735T等位基因增加了EH患者伴发CAS的风险,MMP-3-11716A等位基因增加了汉族EH患者伴发CAS的风险。

Objective To investigate the relationship between the polymorphisms of matrix metalloproteinases and essential hypertension complicated with carotid atherosclerosis.Methods A total of 488 patients with essential hypertension,including 276 Han and 212 Uygur patients,were divided into two groups,CAS group （essential hypertension with carotid atherosclerosis,n=293） and NS group（essential hypertension without carotid atherosclerosis,n=195）.The genotypes were detected with PCR-RFLP technique.The blood pressure and serum lipid levels were determined and the genotypic frequency and the odds ratio （OR） were compared between two groups to study the possible risk factors for carotid atherosclerosis in patients with essential hypertension.Results （1）The frequencies of matrix metalloproteinase-2 TT genotype and T allele and the frequencies of matrix metalloproteinase-3 6A/6A genotype and 6A allele in CAS group were higher than those in NS group（P0.05）.（2） The matrix metalloproteinase-2 -735 CT＋TT allele and matrix metalloproteinase-3 -1171 6A/6A genotypes had an decreased OR in Han patients and a decreased OR in Uygur patients.（3） The binary logistic regression analysis showed that matrix metalloproteinase-2 C-735T genotypes were the risk factors for carotid atherosclerosis in both Han and Uygur patients with essential hypertension.And matrix metalloproteinases-3 -1171 5A/6A homogeneses were the risk factors for carotid atherosclerosis in Han patients with essential hypertension（P0.05）,which had synergism with matrix metalloproteinase.Conclusion Han and Uygur patients have different distribution of matrix metalloproteinase-2 and -3.Matrix metalloproteinase-2 -735 T allele increases the risk for carotid atherosclerosis in both Han and Uygur patients with essential hypertension.Matrix metalloproteinase-2 -1171 6A allele increases the risk for carotid atherosclerosis in Han patients with essential hypertension.