5,10-亚甲基四氢叶酸还原酶C677T基因多态性作为2型糖尿病患者早发冠状动脉疾病的危险因素

5,10-methylenetetrahydrofolate reductase C677T gene polymorphism as a risk factor for premature coronary artery disease in patients with type 2 diabetes mellitus.

作者信息

Mohammed Nisreen O, Ali Ibtisam A, Elamin Bahaelddin K, Saeed Bakri Osman

机构信息

Ahfad Centre for Science and Technology, Ahfad University for Women, Khartoum, Sudan.

Faculty of Medicine, International University of Africa, Khartoum, Sudan.

出版信息

Front Endocrinol (Lausanne). 2025 Jan 22;15:1502497. doi: 10.3389/fendo.2024.1502497. eCollection 2024.

DOI:10.3389/fendo.2024.1502497

PMID:39911235

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11794260/

Abstract

BACKGROUND

Africa, like the rest of the world, is experiencing an increasing prevalence of diabetes mellitus. Diabetes increases the risk for coronary artery disease (CAD) by fourfold compared to people without diabetes. C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) and hyperhomocysteinemia were reported by many studies as risk factors for CAD among patients with type 2 diabetes mellitus (T2DM). Early detection of modifiable risk factors for CAD is an important aspect of management of diabetes. This is the only study in Sudan which investigates the association between MTHFR genotypes and plasma homocysteine levels, and their role in premature CAD (PCAD) among patients with T2DM.

METHODS

This study is a comparative study. We enrolled 226 Sudanese patients with T2DM, age range 25-60 years, recruited from Alshaab and Omdurman teaching hospitals in Khartoum State. 113 patients had CAD confirmed by angiography and electrocardiography (ECG) and 113 had no evidence of CAD. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), using Hinf1 restriction enzyme, were used to determine MTHFR genotypes. Plasma homocysteine levels were determined by enzymatic assay on the Hitachi Cobas Integra 400 plus. Data was analyzed using statistical package for Social Sciences (SPSS) 23, using Mann-Whtney U test, general linear model, Chi-square test and logistic regression analysis.

RESULTS

The frequencies of TT, CT, and CC genotypes were 16,40 and 44% among T2DM patients with PCAD. In T2DM patients without PCAD, the frequencies of TT, CT, and CC genotypes were 00,19 and 83%. The T allele showed strong association with PCAD among T2DM patients, 0.001, odds ratio (OR) 6.2, 95% CI (3.4-11.6). Patients with PCAD showed higher plasma homocysteine levels than patients without PCAD (13.5 µmol/L versus 10 µmol/L, < 0.001). The T allele had significant effect on homocysteine level, (0.001). Plasma homocysteine levels were higher in individuals with TT genotype than those with CT or CC genotypes in patients with PCAD (16.2 + 5.3, 14.3 + 5.7 and 12.9 + 5.02 µmol/L, =0.017). Homocysteine levels showed a significant association with CAD, <0.001, OR 3.2, 95% CI (1.9-5.5).

CONCLUSIONS

Our study suggests that C677T polymorphism of MTHFR gene and hyperhomocysteinemia are risk factors for PCAD in Sudanese population with T2DM.

摘要

背景

与世界其他地区一样，非洲的糖尿病患病率也在不断上升。与非糖尿病患者相比，糖尿病使冠状动脉疾病（CAD）的风险增加了四倍。许多研究报道，亚甲基四氢叶酸还原酶（MTHFR）基因的C677T多态性和高同型半胱氨酸血症是2型糖尿病（T2DM）患者发生CAD的危险因素。早期发现CAD的可改变危险因素是糖尿病管理的一个重要方面。这是苏丹唯一一项研究MTHFR基因分型与血浆同型半胱氨酸水平之间的关联及其在T2DM患者早发性CAD（PCAD）中作用的研究。

方法

本研究为一项对比研究。我们招募了226名年龄在25至60岁之间的苏丹T2DM患者，他们来自喀土穆州的阿尔沙布和恩图曼教学医院。113例患者经血管造影和心电图（ECG）确诊患有CAD，113例患者无CAD证据。采用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）技术，使用Hinf1限制性内切酶来确定MTHFR基因分型。血浆同型半胱氨酸水平通过日立Cobas Integra 400 plus酶法测定。使用社会科学统计软件包（SPSS）23进行数据分析，采用Mann - Whitney U检验、一般线性模型、卡方检验和逻辑回归分析。

结果

在患有PCAD的T2DM患者中，TT、CT和CC基因型的频率分别为16%﹑40%和44%。在无PCAD的T2DM患者中，TT、CT和CC基因型的频率分别为0%﹑19%和83%。在T2DM患者中，T等位基因与PCAD密切相关，P = 0.001，比值比（OR）为6.2，95%置信区间（CI）为（3.4 - 11.6）。患有PCAD的患者血浆同型半胱氨酸水平高于无PCAD的患者（13.5 μmol/L对10 μmol/L，P < 0.001）。T等位基因对同型半胱氨酸水平有显著影响（P = 0.001）。在患有PCAD的患者中，TT基因型个体的血浆同型半胱氨酸水平高于CT或CC基因型个体（16.2 ± 5.3、14.3 ± 5.7和12.9 ± 5.02 μmol/L，P = 0.017）。同型半胱氨酸水平与CAD显著相关，P < 0.001，OR为3.2，95% CI为（1.9 - 5.5）。