Wang Yu, Xu Xin, Huo Yong, Liu Dahai, Cui Yimin, Liu Zeyuan, Zhao Zhigang, Xu Xiping, Liu Lisheng, Li Xiaoying, Jiang Shanqun
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China.
Department of Cardiology, Peking University First Hospital and Medical Department, Beijing, P. R. China.
Clin Appl Thromb Hemost. 2015 Oct;21(7):661-6. doi: 10.1177/1076029613519849. Epub 2014 Jan 22.
To evaluate the performance of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in predicting hyperhomocysteinemia (HHcy) in Chinese patients with hypertension.
We measured plasma total homocysteine tHcy level and C677T genotype in 1058 Chinese patients with hypertension from 4 previous studies. We used 10, 15, and 20 μmol/L as cutoff values for the definition of mild, modest, and severe HHcy, respectively. Logistic models for HHcy were built from the study sample using the C677T genotype as well as age and gender as predictors. The receiver-operating characteristics of the models were evaluated.
Our major findings are that (1) C677T TT genotype is consistently associated with a higher tHcy across the 4 studies, with an increase in size ranging from 38% to 68% in the 4 studies and 51% overall. The C677T polymorphism independently explained about 14% of the total variance of the normalized tHcy. (2) The TT genotype is associated with a large increase in odds ratio (OR) for HHcy. Overall, the multivariate-adjusted ORs for the TT genotype are 3.9 (95% confidence interval [CI]: 2.4-6.4), 6.5 (95% CI: 4.0-10.6), and 17.9 (95% CI: 8.4-38.1) for mild, modest, and severe HHcy, respectively. (3) Overall, the predicting performance increased with HHcy severity, with sensitivity improving from 31.0% for mild HHcy to 70.3% for severe HHcy, and with specificity slightly decreasing from 85.4% to 80.3%. Inclusion of gender and age as predictors significantly improves the sensitivity, especially for predicting mild HHcy.
With an excellent sensitivity and a modest specificity, C677T could be a useful screening marker for severe HHcy.
评估亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态性在中国高血压患者中预测高同型半胱氨酸血症（HHcy）的性能。
我们测量了来自之前4项研究的1058例中国高血压患者的血浆总同型半胱氨酸（tHcy）水平和C677T基因型。我们分别使用10、15和20μmol/L作为轻度、中度和重度HHcy定义的临界值。以C677T基因型以及年龄和性别作为预测因子，从研究样本中建立HHcy的逻辑模型。评估模型的受试者工作特征。
我们的主要发现是：（1）在4项研究中，C677T TT基因型始终与较高的tHcy相关，4项研究中增加幅度从38%到68%不等，总体增加51%。C677T多态性独立解释了标准化tHcy总方差的约14%。（2）TT基因型与HHcy的比值比（OR）大幅增加相关。总体而言，TT基因型的多变量调整OR分别为轻度HHcy的3.9（95%置信区间[CI]：2.4 - 6.4）、中度HHcy的6.5（95%CI：4.0 - 10.6）和重度HHcy的17.9（95%CI：8.4 - 38.1）。（3）总体而言，预测性能随着HHcy严重程度的增加而提高，敏感性从轻度HHcy的31.0%提高到重度HHcy的70.3%，特异性从85.4%略有下降至80.3%。将性别和年龄作为预测因子显著提高了敏感性，尤其是对于预测轻度HHcy。
C677T具有良好的敏感性和适度的特异性，可能是重度HHcy的有用筛查标志物。
