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维生素D受体基因多态性与慢性肾脏病患者心脏病的关联

Association of VDR gene polymorphisms with heart disease in chronic kidney disease patients.

作者信息

Santoro D, Buemi M, Gagliostro G, Vecchio M, Currò M, Ientile R, Caccamo D

机构信息

Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Department of Biomedical Sciences and Morpho-functional Imaging, University of Messina, Messina, Italy.

出版信息

Clin Biochem. 2015 Nov;48(16-17):1028-32. doi: 10.1016/j.clinbiochem.2015.05.009. Epub 2015 May 16.

Abstract

OBJECTIVES

It has been postulated that VDR polymorphisms influence mortality in CKD by directly modifying VDR protein levels or VDR sensitivity in target organs. Here we aimed at evaluating the possible association of VDR FokI and BsmI gene polymorphisms with co-morbid conditions of CKD at different stages.

DESIGN AND METHODS

The patients included in this study were a Sicilian cohort of 171 subjects, at CKD stage 1-2 (n=49), stage 3 (n=34), stage 4-5 (n=34), and hemodialysis (HD) (n=54). Almost 70% of patients were also suffering from heart disease, with/without diabetes and/or hypertension, and 40% were also suffering of hypertension, with/without diabetes and/or heart disease; only around 20% had no co-morbid conditions.

RESULTS

A highly significant association was found between the BsmI B minor allele and heart disease in all CKD stages. Indeed, the odds ratio calculation showed that patients bearing either the bB or BB genotype had, respectively, a seven-fold and around twelve-fold increased risk for heart disease. Instead, the presence of bb wild-type genotype was associated with a fifty-fold reduced risk for heart disease, suggesting that the b allele may display a protective effect. No association was found for FokI genotypes with the different co-morbid conditions.

CONCLUSIONS

We first demonstrated that the VDR BsmI B allele may be considered as a genetic determinant for heart disease and hypertension in CKD, independently from disease stage. Thus, the screening for VDR variants should be regarded as a way to better address preventive strategies and improving the management of CKD co-morbid conditions.

摘要

目的

据推测,维生素D受体(VDR)基因多态性通过直接改变VDR蛋白水平或靶器官中VDR的敏感性来影响慢性肾脏病(CKD)患者的死亡率。在此,我们旨在评估VDR FokI和BsmI基因多态性与不同阶段CKD合并症之间的可能关联。

设计与方法

本研究纳入的患者为西西里岛的171名受试者队列,处于CKD 1 - 2期(n = 49)、3期(n = 34)、4 - 5期(n = 34)以及血液透析(HD)期(n = 54)。近70%的患者还患有心脏病,伴有或不伴有糖尿病和/或高血压,40%的患者患有高血压,伴有或不伴有糖尿病和/或心脏病;只有约20%的患者没有合并症。

结果

在所有CKD阶段,均发现BsmI B次要等位基因与心脏病之间存在高度显著的关联。实际上,优势比计算表明,携带bB或BB基因型的患者患心脏病的风险分别增加了7倍和约12倍。相反,bb野生型基因型的存在与心脏病风险降低50倍相关,这表明b等位基因可能具有保护作用。未发现FokI基因型与不同合并症之间存在关联。

结论

我们首次证明,VDR BsmI B等位基因可能被视为CKD患者心脏病和高血压的遗传决定因素,与疾病阶段无关。因此,筛查VDR变异应被视为一种更好地制定预防策略和改善CKD合并症管理的方法。

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