Klotho G395A基因多态性在非透析慢性肾病患者动脉粥样硬化性心血管疾病和死亡风险评分中的作用

H. Susilo, B. Pikir, M. Thaha, M. Y. Alsagaff, S. D. Suryantoro, C. Wungu, D. S. Budi, Laurentius Andre, Cennikon Pakpahan
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引用次数: 0

摘要

背景:心血管疾病(CVD)是慢性肾脏疾病(CKD)患者死亡的主要原因。CKD患者的Klotho表达降低,导致血管钙化、内皮功能障碍和动脉粥样硬化。我们研究了klotho G395A基因多态性和血浆klotho水平在CKD患者10年动脉粥样硬化性心血管疾病(ASCVD)风险和CVD死亡率中的作用。方法:采用PCR-CTPP法对72例非透析性CKD患者的klotho G395A单核苷酸多态性(SNP)进行基因分型。采用酶联免疫分析法(ELISA)测定klotho水平。通过通路分析确定klotho G395A SNP与血浆klotho水平、ASCVD风险评分、CVD死亡风险评分之间的关系。结果:GA基因型血浆klotho水平低于GG基因型(通径系数=-0.185,p=0.000)。血浆klotho水平与ASCVD危险评分呈显著负相关(r=-0.243, p=0.040),但与CVD死亡危险评分无显著相关(r=-0.145, p=0.225)。通径分析显示,血浆klotho水平对ASCVD危险评分有显著负向直接影响(通径系数=-0.272,p=0.000),对CVD死亡危险评分有间接影响(通径系数=0.187,p=0.005)。结论:Klotho G395A SNP可能降低血浆Klotho水平,从而增加非透析CKD患者ASCVD和CVD死亡风险评分。然而,其他风险因素如年龄、CKD分期、高血压和吸烟也应考虑在内。因此,可以在不同种族群体中进行具有调整变量的大规模遗传关联研究,以获得更稳健的结果。关键词:klotho,单核苷酸多态性,心血管疾病,慢性肾病
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Role of Klotho G395A Gene Polymorphism in Atherosclerotic Cardiovascular Disease and Mortality Risk Scores in Non-dialysis Chronic Kidney Disease
BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Klotho expression was reduced in patients with CKD, leading to vascular calcification, endothelial dysfunction, and atherosclerosis. We investigated the role of the klotho G395A gene polymorphism and plasma klotho level in the ten-year risk of atherosclerotic cardiovascular disease (ASCVD) and CVD mortality in CKD patients.METHODS: We used the PCR-CTPP assay method to genotype klotho G395A single nucleotide polymorphism (SNP) in 72 non-dialysis CKD patients. The klotho level was determined using the enzyme-linked immunoassay (ELISA) method. Path analysis was used to determine the relationship between the klotho G395A SNP, plasma klotho level, ASCVD risk score, and CVD mortality risk score.RESULTS: Our results showed that the GA genotype had lower plasma klotho levels than the GG genotype (path coefficient=-0.185, p=0.000). There was a significant negative correlation between plasma klotho level and the ASCVD risk score (r=-0.243, p=0.040), but no significant correlation was found between plasma klotho level and the CVD mortality risk score (r=-0.145, p=0.225). Path analysis showed that plasma klotho level had a significant negative direct effect on ASCVD risk score (path coefficient=-0.272, p=0.000) and an indirect effect on CVD mortality risk score (path coefficient=0.187, p=0.005).CONCLUSION: Klotho G395A SNP might reduce lower plasma klotho levels, which increased ASCVD and CVD mortality risk scores in non-dialysis CKD patients. However, other risk factors such as age, CKD stages, hypertension, and smoking should be taken into consideration. Therefore, large-scale genetic association studies with adjusted variables could be conducted in various ethnic groups for a more robust result.KEYWORDS: klotho, single nucleotide polymorphism, cardiovascular disease, chronic kidney disease
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