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墨西哥2型糖尿病患者基因变异与代谢及肾功能参数的关联

Association of gene variants with metabolic and renal function parameters in Mexican patients living with type 2 diabetes.

作者信息

Mendoza-Carrera Francisco, Farías-Basulto Alfonso, Gómez-García Erika Fabiola, Rizo de la Torre Lourdes Del Carmen, Cueto-Manzano Alfonso Martin, Cortés-Sanabria Laura, Pérez-Coria Mariana, Vázquez-Rivera Gloria Elizabeth

机构信息

División de Medicina Molecular, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada # 800, Col. Independencia, 44340 Guadalajara, Jalisco Mexico.

Unidad de Medicina Familiar no. 49, IMSS, Guadalajara, Mexico.

出版信息

J Diabetes Metab Disord. 2024 Apr 23;23(1):1125-1131. doi: 10.1007/s40200-024-01398-3. eCollection 2024 Jun.

Abstract

OBJECTIVE

Type 2 diabetes (T2D) and high blood pressure are the main causes of chronic kidney disease (CKD) in adulthood. Both metabolic and oxidative stresses driven by hyperglycemia as well as genetic factors have been suggested as pathogenic causes of renal failure. Some single nucleotide variants (SNVs) on gene coding KLOTHO () have been implicated in several clinical scenarios including hypertension, diabetes, and cardiovascular disease. The aim of this study was to analyze the association of rs1207568 (-395G > A), rs953614 (+ 1062T > G) and rs564481 (+ 1818 C > T) SNVs with metabolic and renal function parameters in Mexican patients living with type 2 diabetes.

METHODS

A cross-sectional study was conducted in 637 Mexican patients with T2D, and/or hypertension without previous diagnosis of CKD. Anthropometric, metabolic, and renal function parameters were determined. Patients were genotyped for rs1207568, rs953614 and rs564481 SNVs and associations under a dominant genetic model were analyzed by logistic regression.

RESULTS

For rs9536314, G-allele showed to be protective for hypo-HDL-C, albuminuria, and CKD. Carriers of minor allele of rs564481 had low odds for high glucose levels. No differences in genotype nor allele frequencies between the patients and the reference population were observed.

CONCLUSION

In Mexican patients living with type 2 diabetes, variant rs9536314 was found associated with low odds of hypo-HDL cholesterol, albuminuria and presence of CKD. Meanwhile the consensus of soluble KLOTHO measurement is reached, genetic variants in the gene could be considered as genetic markers for CKD susceptibility in patients at high-risk of vascular complications.

摘要

目的

2型糖尿病(T2D)和高血压是成年期慢性肾脏病(CKD)的主要病因。高血糖驱动的代谢应激和氧化应激以及遗传因素均被认为是肾衰竭的致病原因。编码KLOTHO()基因上的一些单核苷酸变异(SNV)与包括高血压、糖尿病和心血管疾病在内的多种临床情况有关。本研究的目的是分析rs1207568(-395G>A)、rs953614(+1062T>G)和rs564481(+1818 C>T)单核苷酸变异与墨西哥2型糖尿病患者代谢和肾功能参数之间的关联。

方法

对637例未既往诊断为CKD的墨西哥T2D和/或高血压患者进行了一项横断面研究。测定了人体测量学、代谢和肾功能参数。对患者进行rs1207568、rs953614和rs564481单核苷酸变异的基因分型,并通过逻辑回归分析显性遗传模型下的关联。

结果

对于rs9536314,G等位基因对低高密度脂蛋白胆固醇血症、蛋白尿和CKD具有保护作用。rs564481次要等位基因携带者血糖水平高的几率较低。未观察到患者与参考人群之间基因型和等位基因频率的差异。

结论

在墨西哥2型糖尿病患者中,发现rs9536314变异与低高密度脂蛋白胆固醇血症、蛋白尿和CKD的低几率相关。同时,在可溶性KLOTHO测量达成共识的情况下,KLOTHO基因的遗传变异可被视为血管并发症高危患者CKD易感性的遗传标志物。

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本文引用的文献

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Front Pharmacol. 2022 Sep 21;13:931746. doi: 10.3389/fphar.2022.931746. eCollection 2022.
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Genet Test Mol Biomarkers. 2022 Jul-Aug;26(7-8):382-390. doi: 10.1089/gtmb.2022.0041. Epub 2022 Jul 26.
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Acta Diabetol. 2022 Jun;59(6):803-809. doi: 10.1007/s00592-022-01865-4. Epub 2022 Mar 14.
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Donor Klotho KL-VS Polymorphism Predicts Allograft Glomerulosclerosis and Early Post-Transplant Kidney Function.
Transplant Proc. 2020 Oct;52(8):2371-2375. doi: 10.1016/j.transproceed.2020.02.086. Epub 2020 Jun 20.
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