Yadav Suraj S, Mandal Raju K, Singh Manish K, Verma Archna, Dwivedi Pradeep, Sethi Rishi, Usman Kauser, Khattri Sanjay
1 Department of Pharmacology and Therapeutics, King George's Medical University , Lucknow, India .
DNA Cell Biol. 2014 Nov;33(11):816-22. doi: 10.1089/dna.2014.2511. Epub 2014 Sep 11.
The altered matrix metalloproteinases (MMPs) have been suggested in the pathophysiology of metabolic syndrome (MetS). Genetic variants in the promoter region of MMP1 and MMP9 genes may modulate an individual's susceptibility to MetS. The aim of this study was to determine the frequency of MMP1 -519 A:G and MMP9 -1562 C:T polymorphisms and the correlation with serum levels of MMP1 and MMP9 in MetS susceptibility. On the basis of anthropometric profile and laboratory investigations, 180 confirmed MetS patients and 190 unrelated healthy controls of similar ethnicity were genotyped for MMP1 -519 A:G and MMP9-1562 C:T polymorphisms by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. In addition, serum levels of MMP1 and MMP9 were quantified by ELISA. We found that the serum level of MMP9 was significantly higher in MetS patients. Variant genotype TT of MMP9 -1562 demonstrated increased risk (odds ratio [OR]=3.70, p=0.015) of MetS. Similarly, variant allele T (OR=1.77, p=0.002) and combined genotype CT+TT (OR=1.81, p=0.057) also showed a significantly higher risk. The CT and TT genotypes of MMP9 -1562 polymorphism contributed to high serum levels of MMP9 in MetS patients. However, no such association was observed with the MMP1 serum level and -519 A:G polymorphism. Our results suggest that a higher serum level of MMP9 in the presence of MMP9 polymorphism -1562 C:T might be a risk factor for the development of MetS. The MMP9 enzyme activity might be a significant indicator in the screening of MetS patients.
代谢综合征(MetS)的病理生理学中已提示基质金属蛋白酶(MMPs)发生改变。MMP1和MMP9基因启动子区域的基因变异可能会调节个体对MetS的易感性。本研究的目的是确定MMP1 -519 A:G和MMP9 -1562 C:T多态性的频率以及与MetS易感性中MMP1和MMP9血清水平的相关性。根据人体测量数据和实验室检查结果,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对180例确诊的MetS患者和190例种族相似的无亲缘关系健康对照进行MMP1 -519 A:G和MMP9 -1562 C:T多态性基因分型。此外,通过酶联免疫吸附测定(ELISA)对MMP1和MMP9的血清水平进行定量分析。我们发现MetS患者的MMP9血清水平显著更高。MMP9 -1562的变异基因型TT显示MetS风险增加(比值比[OR]=3.70,p=0.015)。同样,变异等位基因T(OR=1.77,p=0.002)和联合基因型CT+TT(OR=1.81,p=0.057)也显示出显著更高的风险。MMP9 -1562多态性的CT和TT基因型导致MetS患者MMP9血清水平升高。然而,未观察到MMP1血清水平与-519 A:G多态性之间存在此类关联。我们的结果表明,存在MMP9多态性-1562 C:T时较高的MMP9血清水平可能是MetS发生的一个危险因素。MMP9酶活性可能是筛查MetS患者的一个重要指标。