亚甲基四氢叶酸还原酶多态性在健康志愿者中的表现及其与血栓形成患者同型半胱氨酸水平的相关性。

Methylenetetrahydrofolate reductase polymorphism in healthy volunteers and its correlation with homocysteine levels in patients with thrombosis.

机构信息

Department of Clinical Pharmacology, TN Medical College and BYL Nair Hospital, Mumbai, Maharashtra, India.

Department of Hematology, TN Medical College and BYL Nair Hospital, Mumbai, Maharashtra, India.

出版信息

Indian J Pharmacol. 2019 Jul-Aug;51(4):248-254. doi: 10.4103/ijp.IJP_215_19.

DOI:10.4103/ijp.IJP_215_19

PMID:31571711

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6759526/

Abstract

OBJECTIVE

To determine prevalence of methylenetetrahydrofolate reductase (MTHFR) mutations in apparently healthy individuals residing in Mumbai and patients with deep vein thrombosis (DVT) and coronary artery disease (CAD) and to correlate these polymorphisms with homocysteine (Hcy) levels.

MATERIALS AND METHODS

This case-control study was initiated after receiving ethical approval and following the participant's written consent. One hundred and twenty unmatched healthy volunteers and 240 patients with arterial and venous thrombosis were enrolled. The prevalence of C677T and A1298C MTHFR mutations was detected using polymerase chain reaction-restriction fragment length polymorphism technique. Serum Hcy concentration and lipid levels were determined using biochemical kits.

RESULTS

Allele frequency of 677T was 7%, 15%, and 14% in healthy controls, DVT, and CAD patients, respectively, while for 1298C allele, it was 31%, 33%, and 29%, respectively. The lipid markers in CAD patients were significantly low in comparison to the controls while the Hcy level in patients with thrombosis was higher in comparison with the controls. Highest Hcy levels were observed in participants with TT genotype followed by CT genotype and CC genotype in all the three groups. A higher risk of raised Hcy levels was seen in the variants (CT + TT) as compared to CC genotype in DVT (odds ratio [OR] = 3.39, 95% confidence interval [CI] = 1.39-8.2,P < 0.01) and CAD (OR = 21.67, 95%CI = 4.87-96.47,P < 0.0001). The risk observed for A1298C was 2.28 and 2.12 times higher in variants (AC + CC) of both DVT and CAD (OR = 2.28, 95%CI = 1.09-4.75 and OR = 2.12, 95%CI = 1.02-4.40, respectively).

CONCLUSIONS

The prevalence of variants was more in thrombosis patients as compared to unmatched controls. Our study highlights the fact that MTHFR C677T polymorphism as compared to A1298C significantly affects Hcy levels in patients with thrombosis indicating that patients with mutant variants are at higher risk of rapid progression of their disease condition.

摘要

目的

确定孟德尔叶酸还原酶（MTHFR）突变在孟买居住的健康个体、深静脉血栓形成（DVT）和冠心病（CAD）患者中的流行率，并将这些多态性与同型半胱氨酸（Hcy）水平相关联。

材料与方法

本病例对照研究在获得伦理批准并获得参与者书面同意后开始进行。共纳入 120 名不匹配的健康志愿者和 240 名动脉和静脉血栓形成患者。使用聚合酶链反应-限制性片段长度多态性技术检测 C677T 和 A1298C MTHFR 突变的患病率。使用生化试剂盒测定血清 Hcy 浓度和脂质水平。

结果

在健康对照组、DVT 和 CAD 患者中，677T 等位基因频率分别为 7%、15%和 14%，而对于 1298C 等位基因，其频率分别为 31%、33%和 29%。与对照组相比，CAD 患者的脂质标志物显著降低，而血栓形成患者的 Hcy 水平较高。在所有三组中，TT 基因型患者的 Hcy 水平最高，其次是 CT 基因型和 CC 基因型。与 CC 基因型相比，在 DVT（比值比[OR] = 3.39，95%置信区间[CI] = 1.39-8.2，P < 0.01）和 CAD（OR = 21.67，95%CI = 4.87-96.47，P < 0.0001）中，变体（CT + TT）的 Hcy 水平升高的风险更高。在 DVT 和 CAD 中，变体（AC + CC）的风险分别为 2.28 和 2.12 倍（OR = 2.28，95%CI = 1.09-4.75 和 OR = 2.12，95%CI = 1.02-4.40）。