CBS基因甲基化对叶酸干预HHcy效果的性别特异性研究

目的 探究胱硫醚β合成酶(CBS)基因启动子甲基化在不同性别中对叶酸干预高同型半胱氨酸血症(HHcy)效果的影响。 方法 研究对象选自郑州大学第五附属医院住院的1 071例HHcy患者，进行90天的口服叶酸(5 mg/d)干预治疗。根据治疗后复查的血浆同型半胱氨酸(Hcy)水平将患者分为未达标组(Hcy≥15 μmol/L)和达标组(Hcy<15 μmol/L)。运用MethylTargetTM目标区域甲基化测序法检测299例患者CBS基因甲基化水平。运用多因素logistic回归分析CBS基因甲基化在不同性别中对叶酸干预HHcy效果的影响。运用受试者工作特征曲线(ROC)分析CBS基因甲基化在不同性别中对HHcy疗效的预测效果。 结果 CBS基因甲基化水平在两组间的分布差异仅在男性中有统计学意义( t =2.428， P =0.016)。较低水平的CBS基因甲基化在男性中能显著增加叶酸干预HHcy未达标的风险( OR =2.63, 95% CI : 1.41~4.92)。男性患者中CBS基因甲基化与HHcy疗效的ROC曲线下的面积为0.60 (95% CI : 0.52~0.68)。在女性患者中，基因甲基化与HHcy疗效的关联无统计学意义( OR =1.09，95% CI : 0.50~2.37)。 结论 CBS启动子甲基化对叶酸干预HHcy效果的影响存在性别特异性。

Sex-specific effect of CBS gene methylation on the efficacy of folic acid intervention for hyperhomocysteinemia

Abstract: Objective To investigate the effect of cystathionine β synthase ( CBS) gene promoter methylation on the efficacy of folic acid intervention for hyperhomocysteinemia ( HHcy) patients with different genders. Methods 1 071 HHcy patients admitted to the Department of Neurology of the Fifth Affiliated Hospital of Zhengzhou University were selected. They were treated with oral folate ( 5mg /d) for 90 days，and then divided into the standard group ( Hcy ＜ 15 μmol /L) and the substandard group ( Hcy≥15 μmol /L) according to plasma Hcy levels reviewed. The CBS gene methylation levels of 299patients were detected by MethylTargetTM technology. Multivariate logistic regression was used to analyze the effect of CBS gene methylation on the efficacy of folic acid intervention for HHcy in different genders. Receiver operating characteristic( ROC) curve was used to evaluate the predictive effect of CBS gene methylation on the efficacy of HHcy in different genders.Results The distribution difference of CBS methylation levels between the two groups was statistically significant only in males( t = 2. 428，P = 0. 016) . In males，low levels of CBS promoter methylation significantly increased the substandard risk of folic acid intervention for HHcy ( OR = 2. 63，95% CI: 1. 41 ～ 4. 92) . The area under the curve ( AUC) of CBS gene methylation and the efficacy of HHcy in male patients was 0. 60 ( 95% CI: 0. 52 ～ 0. 68) . In female patients，the correlation between CBS gene methylation and the effect of folic acid intervention for HHcy was not statistically significant ( OR = 1. 09，95% CI: 0. 50～ 2. 37) . Conclusion CBS promoter methylation has sex － specific effect on the efficacy of folic acid therapy for patients with HHcy.