2型糖尿病患者基质金属蛋白酶-12基因多态性与缺血性卒中的相关性研究

目的探讨2型糖尿病患者基质金属蛋白酶12(MMP-12)基因多态性与缺血性卒中的相关性。方法选择2013年1月至2015年12月在本科治疗的217例2型糖尿病合并缺血性卒中患者作为病例组,按照TOAST分型结果将病例组患者分为大动脉粥样硬化性卒中(LAA)组88例和非大动脉粥样硬化性卒中(n-LAA)组129例,选择同期在我院体检的无缺血性卒中的2型糖尿病患者100例作为对照组,采用聚合酶链反应-限制性内切酶分析(PCR-RFLP)法比较MMP-12(-82 A/G)和MMP-12(-1082 A/G)基因型多态性在各组间的差异。结果病例组和n-LAA组MMP-12(82 A/G)基因型和等位基因与对照组比较,差异均无统计学意义(P0.05)。LAA组(G/G+A/G)基因型频率显著高于对照组(22.73%vs 11.00%,P=0.031);G等位基因频率也高于对照组(18.18%vs 10.05%,P=0.033)。n-LAA组MMP-12(-1082 A/G)基因型和等位基因与对照组比较,差异均无统计学意义(P0.05)。病例组和LAA组(G/G+A/G)基因型频率均显著高于对照组(33.64%vs 22.00%,P=0.036;37.50%vs 22.00%,P=0.020);两组G等位基因频率也均高于对照组(25.58%vs 17.00%,P=0.017;30.68%vs 17.00%,P=0.002)。多因素Logistic回归分析结果显示MMP-12-82A/G等位基因G和MMP-12-1082A/G等位基因G均是2型糖尿病患者发生LAA的危险因素(OR=1.107,95%CI 1.010-1.371,P=0.031;OR=1.285,95%CI 1.142-1.817,P=0.010)。结论对于2型糖尿病患者,MMP-12基因-82位点G等位基因和-1082位点G基因多态性与大动脉粥样硬化性卒中密切相关。

Association between matrix metalloproteinase-12 gene polymorphisms and ischemic stroke in patients with type 2 diabetes

Objective To investigate the association between matrix metalloproteinase-12 (MMP-12) gene polymorphisms and ischemic stroke in patients with type 2 diabetes.Methods A total of 217 patients with type 2 diabetes complicated by ischemic stroke who were treated in our department from January 2013 to December 2015 were enrolled as case group,and according to the TOAST type,they were divided into large artery atherosclerosis (LAA) group (88 patients) and non-LAA group (n-LAA group,129 patients).A total of 100 patients with type 2 diabetes who had no ischemic stroke and underwent physical examination in our hospital during the same period of time were enrolled as control group.Polymerase chain reaction-restriction fragment length polymorphism was used to measure the differences in MMP-12 (-82 A/G) and MMP-12 (-1082 A/G) gene polymorphisms between groups.Results There were no significant differences in the frequencies of MMP-12 (82 A/G) genotypes and alleles between the case group and the control group,as well as between the n-LAA group and the control group (P ＞ 0.05).Compared with the control group,the LAA group had significantly higher frequencies of (G/G + A/G) genotypes (22.73％ vs 11.00％,P =0.031) and G allele (18.18％ vs 10.05％,P =0.033).There were no significant differences in the frequencies of MMP-12 (-1082 A/G) genotypes and alleles between the n-LAA group and the control group (P ＞ 0.05).Compared with the control group,the case group and the LAA group had significantly higher frequencies of (G/G + A/G) genotypes (33.64％/37.50％ vs 22.00％,P =0.036 and P =0.020) and G allele (25.58％/ 30.68％ vs 17.00％,P =0.017 and P =0.002).The multivariate logistic regression analysis showed that G allele at MMP-12-82A/G (OR =1.107,95％ CI 1.010-1.371,P =0.031) and G allele at MMP-12-1082A/G (OR =1.285,95％ CI 1.142-1.817,P =0.010) were risk factors for the development of LAA in patients with type 2 diabetes.Condusions For patients with type 2 diabetes,gene polymorphisms of G allele in MMP-12 (-82 A/G) and MMP-12 (-1082 A/G) may be closely associated with LAA.