K Jha Chandan, Mir Rashid, Elfaki Imadeldin, Banu Shaheena, Chahal S M S
Department of Human Genetics, Punjabi University, Punjab 147002, India.
Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia.
Med Sci (Basel). 2019 Jul 15;7(7):80. doi: 10.3390/medsci7070080.
Cardiovascular diseases (CVD) are a major cause of death in India and worldwide. Atherosclerosis is caused by the interaction of environmental and genetic factors. Hypercholesterolemia is an example of a classical risk factor for CVD. The low-density lipoprotein receptor (LDLR) is one of the regulating mechanisms the liver uses for cholesterol homeostasis. Gene variations in the LDLR have been reported to cause hypercholesterolemia and consequently CVD. We investigated the association of polymorphisms in the LDLR (rs5925 and rs1529729) with coronary artery disease (CAD) in 200 coronary artery disease patients and 200 matched healthy controls using allele-specific PCR (AS-PCR). The results indicated that the CT genotype of the rs1529729 polymorphism was associated a decreased susceptibility to CAD with an odds ratio (OR) = 0.42 (95% confidence interval (CI), 0.23-0.77), risk ratio (RR) = 0.59 (0.39-0.89), = 0.0047. The TT genotype of the rs1529729 polymorphism was also associated with decreased susceptibility to CAD with an OR = 0.19 (95% CI, 0.076-0.47), RR = 0.57 (0.47-0.69), = 0.0003. The GA genotype of the rs5925 polymorphism was associated with decreased susceptibility to CAD with an OR = 0.45 (95% CI, 0.27-0.75), RR = 0.65 (0.47-0.88), = 0.002. We concluded that the CT and TT genotypes of the rs1529729 polymorphism and the GA genotype of the rs5925 polymorphism are probably associated with decreased susceptibility to CAD. The simplicity of AS-PCR makes it particularly suitable for the rapid, large-scale screening of gene variabilities in the LDLR. AS-PCR could provide significant benefits in clinical applications with its ability to amplify a lower quantity of samples in a cost-saving manner. Nevertheless, these findings need to be validated in well-designed studies with larger sample sizes and in different populations.
心血管疾病（CVD）是印度乃至全球主要的死亡原因。动脉粥样硬化是由环境因素和遗传因素相互作用引起的。高胆固醇血症是CVD的典型风险因素之一。低密度脂蛋白受体（LDLR）是肝脏用于维持胆固醇稳态的调节机制之一。据报道，LDLR基因变异会导致高胆固醇血症，进而引发CVD。我们使用等位基因特异性PCR（AS-PCR），对200例冠心病（CAD）患者和200例匹配的健康对照者进行研究，以调查LDLR基因多态性（rs5925和rs1529729）与CAD的关联。结果表明，rs1529729多态性的CT基因型与CAD易感性降低相关，优势比（OR）= 0.42（95%置信区间（CI），0.23 - 0.77），风险比（RR）= 0.59（0.39 - 0.89），P = 0.0047。rs1529729多态性的TT基因型也与CAD易感性降低相关，OR = 0.19（95% CI，0.076 - 0.47），RR = 0.57（0.47 - 0.69），P = 0.0003。rs5925多态性的GA基因型与CAD易感性降低相关，OR = 0.45（95% CI，0.27 - 0.75），RR = 0.65（0.47 - 0.88），P = 0.002。我们得出结论，rs1529729多态性的CT和TT基因型以及rs5925多态性的GA基因型可能与CAD易感性降低相关。AS-PCR操作简便，特别适合对LDLR基因变异进行快速、大规模筛查。AS-PCR能够以节省成本的方式扩增少量样本，在临床应用中可能具有显著优势。然而，这些发现需要在样本量更大的精心设计研究以及不同人群中进行验证。
