乌干达一家三级医院2型糖尿病患者ACE基因多态性的分布及其与肾病生物标志物和代谢指标的关联

Distribution of the ACE Gene Polymorphisms in Type 2 Diabetes Mellitus Patients, Their Associations with Nephropathy Biomarkers and Metabolic Indicators at a Tertiary Hospital in Uganda.

作者信息

Kiconco Ritah, Kalyesubula Robert, Kiwanuka Gertrude N

机构信息

Department of Medical Laboratory Science, Mbarara University of Science and Technology, Mbarara, Uganda.

Department of Biochemistry, Soroti University, Soroti, Uganda.

出版信息

Diabetes Metab Syndr Obes. 2024 Jun 5;17:2211-2220. doi: 10.2147/DMSO.S462740. eCollection 2024.

DOI:10.2147/DMSO.S462740

PMID:38854447

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11162639/

Abstract

PURPOSE

We aimed at determining the distribution of the ACE insertion/deletion gene polymorphisms among type 2 diabetic patients and their association with the nephropathy biomarkers and the metabolic indicators.

PATIENTS AND METHODS

Data were collected from 237 adult type 2 diabetes mellitus patients receiving healthcare at the diabetic clinic of Mbarara Regional Referral Hospital. Peripheral blood genomic DNA was amplified using a conventional PCR technique and analyzed for the ACE homozygous forms of the insertion (II), deletion (DD) and heterozygous insertion deletion (ID) genotypes as well as their respective allele counts. Biomarkers of nephropathy were analyzed on a Beckman coulter AU480 chemistry analyzer using system compatible reagents.

RESULTS

Majority of the participants were older persons (Median = 57, IQR = 49-64) and female 171 (72.2%). Most of them had the Deletion allele 198 (83.5%) and DD genotype 116 (48.9%). At multivariate logistic regression, the nephropathy biomarkers that is microalbuminuria, serum creatinine, urea, eGFR and electrolytes had no association with the ACE I/D alleles or genotypes (p > 0.05). On the other hand, selected metabolic indicators had a positive relationship. The insertion allele was associated with increasing glycated hemoglobin (OR = 1.082, p = 0.019) and decreasing serum glucose levels (OR = 0.891, p = 0.001). Deletion allele was associated with decreasing glycated hemoglobin (OR = 0.924, p = 0.047) and increasing serum glucose levels (OR = 1.208, p = 0.001). ACE II genotype was associated with decreasing serum glucose levels (OR = 0.873, p = 0.029). ACE DD genotype was associated with decreasing glycated hemoglobin (OR = 0.917, p = 0.010) and increasing serum glucose levels (OR = 1.132, p = 0.001). ACE ID genotype was associated with increasing glycated hemoglobin (OR = 1.077, p = 0.022), triglyceride levels (OR = 1.316, p = 0.031) and decreasing serum glucose levels (OR = 0.933, p = 0.038).

CONCLUSION

The presence or absence of the ACE I/D alleles and genotypes affects the ultimate increase or decrease in the serum glucose, glycated hemoglobin and triglyceride levels. Although there was no significant association between the biomarkers of nephropathy and the ACE I/D alleles or genotypes, the above implicated metabolic indicators should be included in healthcare guidelines used when attending to type 2 diabetic patients.

摘要

目的

我们旨在确定2型糖尿病患者中血管紧张素转换酶（ACE）插入/缺失基因多态性的分布情况，以及它们与肾病生物标志物和代谢指标之间的关联。

患者与方法

收集了在姆巴拉拉地区转诊医院糖尿病诊所接受治疗的237例成年2型糖尿病患者的数据。使用传统PCR技术扩增外周血基因组DNA，并分析ACE基因纯合子形式的插入（II）、缺失（DD）和杂合子插入缺失（ID）基因型以及它们各自的等位基因计数。使用系统兼容试剂在贝克曼库尔特AU480化学分析仪上分析肾病生物标志物。

结果

大多数参与者为老年人（中位数 = 57，四分位间距 = 49 - 64），女性有171例（72.2%）。他们中的大多数具有缺失等位基因198例（83.5%）和DD基因型116例（48.9%）。在多因素逻辑回归分析中，肾病生物标志物，即微量白蛋白尿、血清肌酐、尿素、估算肾小球滤过率（eGFR）和电解质，与ACE I/D等位基因或基因型无关联（p > 0.05）。另一方面，所选的代谢指标存在正相关关系。插入等位基因与糖化血红蛋白升高相关（比值比 = 1.082，p = 0.019），与血清葡萄糖水平降低相关（比值比 = 0.891，p = 0.001）。缺失等位基因与糖化血红蛋白降低相关（比值比 = 0.924，p = 0.047），与血清葡萄糖水平升高相关（比值比 = 1.208，p = 0.001）。ACE II基因型与血清葡萄糖水平降低相关（比值比 = 0.873，p = 0.029）。ACE DD基因型与糖化血红蛋白降低相关（比值比 = 0.917，p = 0.010），与血清葡萄糖水平升高相关（比值比 = 1.132，p = 0.001）。ACE ID基因型与糖化血红蛋白升高相关（比值比 = 1.077，p = 0.022）、甘油三酯水平升高相关（比值比 = 1.316，p = 0.031）以及血清葡萄糖水平降低相关（比值比 = 0.933，p = 0.038）。