Annals of clinical and laboratory science · 2019
Significant Association of Methylenetetrahydrofolate dehydrogenase 1 Promoter Hypomethylation with Stroke in a Chinese Population with Primary Hypertension.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wang Changyi, Xu Guodong, Wen Qi, Peng Xiaolin, Chen Hongen, Zhang Jingwen, Xu Shan, Zhang Chunhui, Zhang Min, Ma Jianping, Hui Zhaohui, Du Jianhang, Wu Guifu, Ma Min
Аннотация
OBJECTIVE: Hypertension and hyperhomocysteinemia are both stroke risk factors. Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) plays a vital role in one-carbon metabolism via encoding a protein with three distinct enzymatic activities (methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate cyclohydrolase, and formate-tetrahydrofolate ligase). We aimed to elucidate the association between MTHFD1 promoter methylation and stroke in a Chinese population with primary hypertension.
METHODS: Quantitative methylation-specific PCR was used to quantify MTHFD1 methylation levels in 243 hypertensive controls and 138 matched patients with stroke (also with primary hypertension). A luciferase reporter gene assay was performed to investigate the possible regulatory function of the MTHFD1 promoter.
RESULTS: Methylation of the MTHFD1 promoter was significantly higher in hypertensive controls than in patients with stroke (median [interquartile range]: 10.16[6.61-14.00] vs. 5.41[3.15-7.53], P<0.001). The median level of homocysteine (Hcy) was 15.50 μmol/L in patients with stroke, which was higher than the (homocysteine) Hcy level of 14.40 μmol/L in the hypertensive controls (P=0.010). The diagnostic value of MTHFD1 methylation for stroke was also examined. The area under the curve was 0.789(0.743-0.836), and the sensitivity and specificity were 79.7% and 67.1%, respectively. A significant inverse correlation was observed between MTHFD1 methylation level and Hcy (rs =-0.110, P=0.031). Subsequently, a significant gene regulatory function of the MTHFD1 promoter was discovered using a dual-luciferase reporter assay.
CONCLUSIONS: Our findings suggest a significant association between hypomethylation of the MTHFD1 promoter and stroke in Chinese hypertensive populations.
METHODS: Quantitative methylation-specific PCR was used to quantify MTHFD1 methylation levels in 243 hypertensive controls and 138 matched patients with stroke (also with primary hypertension). A luciferase reporter gene assay was performed to investigate the possible regulatory function of the MTHFD1 promoter.
RESULTS: Methylation of the MTHFD1 promoter was significantly higher in hypertensive controls than in patients with stroke (median [interquartile range]: 10.16[6.61-14.00] vs. 5.41[3.15-7.53], P<0.001). The median level of homocysteine (Hcy) was 15.50 μmol/L in patients with stroke, which was higher than the (homocysteine) Hcy level of 14.40 μmol/L in the hypertensive controls (P=0.010). The diagnostic value of MTHFD1 methylation for stroke was also examined. The area under the curve was 0.789(0.743-0.836), and the sensitivity and specificity were 79.7% and 67.1%, respectively. A significant inverse correlation was observed between MTHFD1 methylation level and Hcy (rs =-0.110, P=0.031). Subsequently, a significant gene regulatory function of the MTHFD1 promoter was discovered using a dual-luciferase reporter assay.
CONCLUSIONS: Our findings suggest a significant association between hypomethylation of the MTHFD1 promoter and stroke in Chinese hypertensive populations.