2 型糖尿病中国患者胰岛淀粉样变与载脂蛋白 E 多态性的组织病理学相关性。

Histopathological correlations of islet amyloidosis with apolipoprotein E polymorphisms in type 2 diabetic Chinese patients.

机构信息

From the Departments of *Medicine and Therapeutics, and †Anatomical and Cellular Pathology, Prince of Wales Hospital, ‡Hong Kong Institute of Diabetes and Obesity, and §Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.

出版信息

Pancreas. 2013 Oct;42(7):1129-37. doi: 10.1097/MPA.0b013e3182965e6e.

DOI:10.1097/MPA.0b013e3182965e6e

PMID:24005233

Abstract

OBJECTIVE

Islet amyloidosis and arteriosclerosis are histopathological hallmarks in type 2 diabetes. Apolipoprotein E (ApoE) is a common component of amyloidosis. ApoE [Latin Small Letter Open E]4 allele is associated with arteriosclerosis and cerebral amyloidosis in Alzheimer disease. We examined the correlations of ApoE polymorphisms with islet amyloidosis in type 2 diabetes.

METHODS

Genomic DNA samples were obtained from 117 autopsy cases with type 2 diabetes and 209 nondiabetic cases. ApoE genotypes and amylin gene mutations were determined by polymerase chain reaction-ligase detection reaction analysis. Islet amyloidosis and arteriosclerosis were evaluated by staining of thioflavin T, amylin, ApoE, and amyloid P component.

RESULTS

In the diabetic group, 33.3% in group [Latin Small Letter Open E]2 ([Latin Small Letter Open E]2[Latin Small Letter Open E]2, [Latin Small Letter Open E]2[Latin Small Letter Open E]3), 23.6% in group [Latin Small Letter Open E]3 ([Latin Small Letter Open E]3[Latin Small Letter Open E]3), and 62.5% in group [Latin Small Letter Open E]4 ([Latin Small Letter Open E]4[Latin Small Letter Open E]4, [Latin Small Letter Open E]3[Latin Small Letter Open E]4) had islet amyloidosis. After adjustment for confounders, group [Latin Small Letter Open E]4 had an odds ratio of 7.0 (95% confidence interval, 1.3-38.0; P = 0.023) in having islet amyloidosis compared to group [Latin Small Letter Open E]3. Diabetic cases with islet amyloidosis had more severe arteriosclerosis (P = 0.0111), arteriolar hyalinosis (P = 0.0369), and interstitial fibrosis (P = 0.0188) than those without amyloidosis. Immunoreactivity of both ApoE and amyloid P component was detected in islet amyloid deposits and arteriosclerotic lesions.

CONCLUSIONS

In type 2 diabetes, islet amyloidosis and arteriosclerosis share common pathophysiological features with ApoE [Latin Small Letter Open E]4 as a probable linking factor.

摘要

目的

胰岛淀粉样变和动脉硬化是 2 型糖尿病的组织病理学特征。载脂蛋白 E（ApoE）是淀粉样变的常见成分。载脂蛋白 E [小写拉丁字母开 E]4 等位基因与阿尔茨海默病中的动脉硬化和脑淀粉样变有关。我们研究了载脂蛋白 E 多态性与 2 型糖尿病中胰岛淀粉样变的相关性。

方法

从 117 例 2 型糖尿病尸检病例和 209 例非糖尿病病例中获得基因组 DNA 样本。通过聚合酶链反应-连接酶检测反应分析确定载脂蛋白 E 基因型和胰岛淀粉样多肽基因突变。通过硫代黄素 T、胰岛淀粉样多肽、载脂蛋白 E 和淀粉样蛋白 P 成分染色评估胰岛淀粉样变和动脉硬化。

结果

在糖尿病组中，[小写拉丁字母开 E]2 组（[小写拉丁字母开 E]2[小写拉丁字母开 E]2、[小写拉丁字母开 E]2[小写拉丁字母开 E]3）的 33.3%、[小写拉丁字母开 E]3 组（[小写拉丁字母开 E]3[小写拉丁字母开 E]3）的 23.6%和[小写拉丁字母开 E]4 组（[小写拉丁字母开 E]4[小写拉丁字母开 E]4、[小写拉丁字母开 E]3[小写拉丁字母开 E]4）的 62.5%有胰岛淀粉样变。在调整混杂因素后，与[小写拉丁字母开 E]3 组相比，[小写拉丁字母开 E]4 组发生胰岛淀粉样变的比值比为 7.0（95%置信区间，1.3-38.0；P=0.023）。有胰岛淀粉样变的糖尿病病例的动脉硬化（P=0.0111）、小动脉玻璃样变（P=0.0369）和间质纤维化（P=0.0188）程度更严重。胰岛淀粉样沉积物和动脉硬化病变中均检测到载脂蛋白 E 和淀粉样蛋白 P 成分的免疫反应性。