Suppr
超能文献

巨核细胞载脂蛋白单核苷酸多态性变异与大血管病变相关，而基质金属蛋白酶-9 单核苷酸多态性转换可能预示 2 型糖尿病患者糖尿病肾病的易感性。

Cubilin Single Nucleotide Polymorphism Variants are Associated with Macroangiopathy While a Matrix Metalloproteinase-9 Single Nucleotide Polymorphism Flip-Flop may Indicate Susceptibility of Diabetic Nephropathy in Type-2 Diabetic Patients.

机构信息

Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University, Magdeburg, Germany,

Diaverum Deutschland, Potsdam, Germany,

出版信息

Nephron. 2019;141(3):156-165. doi: 10.1159/000494391. Epub 2018 Dec 17.

DOI:10.1159/000494391

PMID:30557881

Abstract

AIM

Aim of this study was to investigate the association of genetic variants of functional polymorphisms of matrix metalloproteinase and Cubilin (CUBN) with diabetic nephropathy (DN), end-stage renal disease (ESRD), and risk of cardiovascular disease (CVD) in Caucasian type 2 diabetes (T2D) patients.

METHODS

472 T2D-patients were genotyped for 3 single-nucleotide polymorphisms (SNPs; MMP-2 [rs2285053], MMP-9 [rs17576] and CUBN [rs1801239]). Genotyping was carried out by allelic discrimination using TaqMan SNP-genotyping-assay.

RESULTS

MMP-9 (Gln279Arg) AA-genotype (OR 0.17 [0.04-0.62, p = 0.008]) and the time elapsed since diagnosis of T2D without onset of proteinuria (OR 0.87 [0.79-0.97, p = 0.008]) were found to be independently associated with reduced risk of susceptibility to DN. On the contrary higher stages of chronic kidney disease (OR 1.93 [1.15-3.23], p = 0.012) and the presence of MMP-9 GG-genotype were independently associated with DN (OR 6.07 [1.60-22.99], p = 0.008). The CUBN CC or C-risk-allele of rs1801239 was associated with ESRD (OR 2.04 [1.07-3.87], p = 0.03) and peripheral artery disease (OR 2.08 [1.12-3.88], p = 0.021). We could not find an association with MMP-2, MMP-9, or CUBN with CVD in a composite clinical endpoint model.

CONCLUSIONS

This study highlights that MMP-9 or CUBN-SNPs may exert effects on risk of susceptibility to DN or ESRD. We provide novel evidence on genetic susceptibility for macroangiopathy in patients with a missense variant of CUBN (Ile2984Val) in patients with T2D.

摘要

目的

本研究旨在探讨基质金属蛋白酶和 Cubilin（CUBN）功能多态性的遗传变异与高加索 2 型糖尿病（T2D）患者糖尿病肾病（DN）、终末期肾病（ESRD）和心血管疾病（CVD）风险之间的关系。

方法

对 472 名 T2D 患者进行了 3 个单核苷酸多态性（SNP；MMP-2 [rs2285053]、MMP-9 [rs17576]和 CUBN [rs1801239]）的基因分型。采用 TaqMan SNP 基因分型分析进行等位基因鉴别。

结果

MMP-9（Gln279Arg）AA 基因型（OR 0.17 [0.04-0.62，p = 0.008]）和 T2D 确诊后未出现蛋白尿的时间（OR 0.87 [0.79-0.97，p = 0.008]）与降低 DN 易感性的风险独立相关。相反，慢性肾脏病（CKD）的较高阶段（OR 1.93 [1.15-3.23]，p = 0.012）和 MMP-9 GG 基因型的存在与 DN 独立相关（OR 6.07 [1.60-22.99]，p = 0.008）。rs1801239 的 CUBN CC 或 C 风险等位基因与 ESRD（OR 2.04 [1.07-3.87]，p = 0.03）和外周动脉疾病（OR 2.08 [1.12-3.88]，p = 0.021）独立相关。我们在复合临床终点模型中未发现 MMP-2、MMP-9 或 CUBN 与 CVD 之间存在关联。