慢性肾脏病中基质Gla蛋白和一氧化氮合酶-3基因变异及其与心血管风险的关系

Matrix Gla Protein and Nitric Oxide Synthase-3 Genetic Variants in Chronic Kidney Disease and Their Relation with Cardiovascular Risk.

作者信息

Priyadarshini G, Parameswaran Sreejith, Sahoo Jayaprakash, Selvarajan Sandhiya, Ramesh Ananthakrishnan, Rajappa Medha

机构信息

Department of Biochemistry Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

Department of Nephrology Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

出版信息

Int J Nephrol. 2024 Aug 30;2024:3850055. doi: 10.1155/2024/3850055. eCollection 2024.

DOI:10.1155/2024/3850055

PMID:39246453

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11379508/

Abstract

BACKGROUND

Chronic kidney disease (CKD) is defined by gradual deterioration of renal parenchyma and decline of functioning nephrons. The risk of cardiovascular events is drastically increased in patients with CKD. This complicated link of CKD and cardiovascular disease (CVD) is not well understood till date.

OBJECTIVE

We aim to study the influence of genetic variants of matrix Gla protein () gene rs1800801, rs1800802, and rs4236 and nitric oxide synthase-3 () gene rs1799983 and rs2070744 on the risk of CKD and its associated cardiovascular comorbidity in South Indian Tamils.

METHODS

One hundred and eighty-five CKD patients and 185 controls were recruited in this research. Flow-mediated dilatation (FMD) of brachial artery was measured ultrasonically. Circulating levels of MGP and nitric oxide (NO) were measured by ELISA. Genotyping was done by real-time PCR.

RESULTS

We observed a significant difference in the distribution of TT and CT genotypes of (rs2070744), indicating an increase in the risk of CKD. NO level was significantly decreased in CKD cases than controls. We also found a significant difference in the distribution of TTA and CCG haplotypes of polymorphisms (1-rs4236; 2-rs1800801; 3-rs1800802) between the groups, indicating an increase in the risk of CKD. CT genotype of MGP (rs4236) and CT genotype of NOS3 (rs2070744) variants were found to be associated with decreased FMD, indicating endothelial dysfunction, the harbinger of CVD.

CONCLUSION

We conclude that genetic variants of and enhance the risk of CKD and its associated cardiovascular comorbidity in South Indian Tamils.

摘要

背景

慢性肾脏病（CKD）的定义是肾实质逐渐恶化以及功能性肾单位数量减少。CKD患者发生心血管事件的风险急剧增加。迄今为止，CKD与心血管疾病（CVD）之间这种复杂的联系尚未得到充分理解。

目的

我们旨在研究基质Gla蛋白（MGP）基因rs1800801、rs1800802和rs4236以及一氧化氮合酶-3（NOS3）基因rs1799983和rs2070744的基因变异对南印度泰米尔人CKD风险及其相关心血管合并症的影响。

方法

本研究招募了185例CKD患者和185名对照。通过超声测量肱动脉的血流介导的扩张（FMD）。采用酶联免疫吸附测定法（ELISA）测量循环中MGP和一氧化氮（NO）的水平。通过实时聚合酶链反应（PCR）进行基因分型。

结果

我们观察到NOS3（rs2070744）的TT和CT基因型分布存在显著差异，表明CKD风险增加。CKD患者的NO水平显著低于对照组。我们还发现两组之间MGP多态性（1-rs4236；2-rs1800801；3-rs1800802）的TTA和CCG单倍型分布存在显著差异，表明CKD风险增加。发现MGP（rs4236）的CT基因型和NOS3（rs2070744）变异的CT基因型与FMD降低有关，表明存在内皮功能障碍，这是CVD的先兆。