背景:冠状动脉疾病(CAD)是心肌梗死(MI)的主要原因。然而,它们的潜在病因可以在环境因素和遗传因素之间的相互作用中找到。另一方面,它已经表明,细胞外基质(ECM)蛋白,如血小板反应素(TSP),在血管病变中起着至关重要的调节作用,包括动脉粥样硬化.TSP是负责细胞间和细胞-ECM相互作用的细胞外蛋白,并参与调节功能反应。最近,据报道,TSP-4基因的错义突变可能会增加患CADs的风险.本研究旨在研究rs1866389鸟苷对TSP-4基因的胞嘧啶(G/C)单核苷酸多态性(SNP)在伊朗南部过早MI患病率中的作用。
方法:本病例对照研究包括100例早产儿MI患者和100例健康个体。从参与者的血液样本中提取的DNA进行了TSP-4基因序列的聚合酶链反应(PCR)。之后,在病例组和对照组中评估了TSP-4基因的C(突变)和G(正常)等位基因的频率。
结果:根据我们的发现,性别差异无统计学意义,年龄,和吸烟状况。然而,病例组的糖尿病(DM)患病率明显更高,高脂血症(HLP),和高血压(HTN)与对照组相比。此外,22%,49%,29%的病例组患有CC,GC,和TSP-4基因中的GG基因型,分别,而CC的患病率,GC,GG基因型为10%,44%,对照组为46%。此外,等位基因C的患病率在病例组(47%)明显高于对照组(33%,P=0.043),显示其与过早MI风险增加显著相关(OR=1.80;95%CI=1.01-3.19)。
结论:TSP-4基因的rs1866389G/CSNP显著增加了伊朗南部人群过早心肌梗死的风险。因此,这种突变的基因可以用作基因治疗的靶标或早期检测处于高CADs风险的个体的标记。
BACKGROUND: Coronary Artery Diseases (CAD) are the leading cause of Myocardial Infarction (MI). However, their underlying etiology can be found in the interplay between environmental and genetic factors. On the other hand, it has been shown that Extracellular Matrix (ECM) proteins, such as Thrombospondins (TSP), play a crucial regulatory role in vascular pathologies, including atherogenesis. TSPs are extracellular proteins responsible for intercellular and cell-ECM interactions and are involved in regulating functional responses. Recently, a missense mutation in the TSP-4 gene has been reported to potentially increase the risk of CADs. The present study aimed to investigate the role of rs1866389 Guanosine to Cytosine (G/C) Single Nucleotide Polymorphism (SNP) of the TSP-4 gene on the prevalence of premature MI in southern Iran.
METHODS: The present case-control study included 100 patients with premature MI and 100 healthy individuals. The DNA extracted from the blood samples of the participants underwent Polymerase Chain Reaction (PCR) for the sequence of the TSP-4 gene. Afterward, the frequency of C (mutated) and G (normal) alleles of the TSP-4 gene was evaluated in the case and control groups.
RESULTS: According to our findings, there was no significant intergroup difference in gender, age, and smoking status. However, the case group was significantly higher in the prevalence of Diabetes mellitus (DM), Hyperlipidemia (HLP), and Hypertension (HTN) compared to the control group. Moreover, 22%, 49%, and 29% of the case group had CC, GC, and GG genotypes in the TSP-4 gene, respectively, while the prevalence of CC, GC, and GG genotypes were 10%, 44%, and 46% in the control group. Also, the prevalence of allele C was significantly higher in the case group (47%) compared to the control group (33%, P=0.043), showing its significant association with the increased risk of premature MI (OR = 1.80; 95% CI = 1.01-3.19).
CONCLUSIONS: The rs1866389 G/C SNP of the TSP-4 gene significantly increased the risk of premature MI in the population of southern Iran. Thus, such mutated gene can be used as a target for gene therapy or a marker for early detection of individuals at high risk for CADs.