Efficacy of Folic Acid Therapy in Patients with Hyperhomocysteinemia

Tian, Huizi; Tian, Dean; Zhang, Chengda; Wang, Wenhua; Wang, Lianke; Ge, Mengying; Hou, Quanliang; Zhang, Weidong

doi:10.1080/07315724.2017.1330162

Cited by 23 publications

(17 citation statements)

References 32 publications

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“…Currently, folate supplementation is the primary intervention in HHcy therapy, which can effectively reduce plasma Hcy in China. 5 In our preliminary research, 6 the Hcy levels of over 40% of patients were still higher than 15 μmol/l after 90 days of 5 mg/day folate intervention.…”

Section: Introductionmentioning

confidence: 71%

“…Compliance was assessed by telephone interview at 45 and 90 days of follow‐up. Our preliminary study found that there was significant difference in the effective rate among 858 HHcy patients (175 cases who lost to follow‐up or with poor compliance were excluded) with good and moderate compliance . Subjects were divided into the success group (Hcy < 15 μmol/l) and failure group (Hcy ≥ 15 μmol/l) according to the reviewed Hcy levels.…”

Section: Methodsmentioning

confidence: 99%

“…Our preliminary study found that there was significant difference in the effective rate among 858 HHcy patients (175 cases who lost to follow-up or with poor compliance were excluded) with good and moderate compliance. 6 Subjects were divided into the success group (Hcy < 15 μmol/l) and failure group (Hcy ≥ 15 μmol/l) according to the reviewed Hcy levels. The study was approved by the Ethics Review Committee of the Life Science of Zhengzhou University.…”

Section: Study Population and Designmentioning

confidence: 99%

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CBS gene polymorphism and promoter methylation‐mediating effects on the efficacy of folate therapy in patients with hyperhomocysteinemia

Zhao

Zhang

et al. 2020

The Journal of Gene Medicine

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Background A decrease in cystathionine beta‐synthase (CBS) enzyme activity could lead to hyperhomocysteinemia (HHcy). Studies have revealed that DNA methylation has a mediating effect on the development of diseases. The present study aimed to explore CBS promoter methylation‐mediating effects on the efficacy of folate treatment for HHcy. Methods HHcy patients were treated with folate (5 mg/day) for 90 days and then divided into a failure group (Hcy ≥ 15 μmol/l) and a success group (Hcy < 15 μmol/l) according to post‐treatment plasma Hcy levels. Genotyping of CBS gene (rs2851391 and rs706209) in patients (n = 638) was detected using a MassArray system (Sequenom, San Diego, CA, USA). The baseline DNA methylation levels of patients (n = 299) were detected using MethylTarget™ technology (Genesky Biotechnologies Inc., Shanghai, China). Results The CBS rs2851391 TC + CC genotype was related to a 57% reduction of failure risk in HHcy treatment compared to the TT genotype (95% confidence interval [CI] = 0.19–0.97). The CBS rs706209 CT + TT genotype had a 2.97‐fold increased risk of failure to treatment compared to the CC genotype (95% CI = 1.52–5.80). After adjustment for confounding factors, the odds ratio (95% CI) for the risk of failure in HHcy treatment in total and male patients was 0.55 (0.32–0.93) and 0.34 (0.16–0.69), respectively, for patients with higher methylation levels (≥ methylation median). Additionally, baseline CBS promoter methylation mediated 33.39% of the effect of rs2851391 on the efficacy of folate treatment for HHcy (ACME [average causal mediation effects]: –0.05, 95% CI = –0.11 to 0.00, p = 0.046). Conclusions The present study indicates that CBS gene polymorphism and promoter methylation could affect the efficacy of HHcy. There were potentially causal effects of genetic, epigenetic variations at the CBS rs2851391 locus on the efficacy of HHcy therapy with folate.

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Section: Introductionmentioning

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Study Population and Designmentioning

confidence: 99%

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CBS gene polymorphism and promoter methylation‐mediating effects on the efficacy of folate therapy in patients with hyperhomocysteinemia

Zhao

Zhang

et al. 2020

The Journal of Gene Medicine

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“…According to the formation mechanism of HHcy, the current expert guidelines recommend folic acid and vitamin B12 supplementation for treatment [8][9][10][11][12], but meta-analysis results show that folic acid supplementation for more than three years is necessary to reduce the risk of stroke [13].…”

Section: Introductionmentioning

confidence: 99%

Effect of Moxibustion on Hyperhomocysteinemia and Oxidative Stress Induced by High‐Methionine Diet

Wang

Hui

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. The aim of this study was to assess the effects of moxibustion on the animal model of oxidative stress and cardiovascular injury induced by high-methionine diet (2% methionine and 3.5% fat on the basis of ordinary maintenance feed) during 12 weeks. Methods. 53 mice were divided into four groups: mice in the Control group (n = 8), mice in the Met group (n = 15), mice in the Met + Moxibustion group (n = 15), and mice in the Met + Smoke group (n = 15). After 12 weeks of intervention, homocysteine (Hcy), S-adenosine homocysteine (SAH), superoxide dismutase (SOD), oxygenized low-density lipoprotein (ox-LDL), endothelial nitric oxide synthase (eNOS), and heme oxygenase-1 (HO-1) were determined in the serum and aortic homogenate. Results. Compared with the Met group, our results indicated that through moxibustion intervention, the content of serum Hcy and its intermediate metabolite SAH can be reduced to a certain extent, and SOD, HO-1, and ox-LDL can be increased. Conclusion. This study showed moxibustion’s ability to enhance the body’s antioxidation and protect vascular endothelial function, thus playing an early role in the prevention and treatment of atherosclerosis.

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“…At home and abroad, the results of the study on supplementation of folic acid to reduce Hcy concentration were inconsistent (13)(14)(15) . A previous study found that more than 40 % patients with HHcy failed to reach the normal level after folic acid supplementation (16) . These may be caused by genetics.…”

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confidence: 99%

Prediction model for the efficacy of folic acid therapy on hyperhomocysteinaemia based on genetic risk score methods

Zhang

Liu

et al. 2019

Br J Nutr

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No risk assessment tools for the efficacy of folic acid treatment for hyperhomocysteinaemia (HHcy) have been developed. We aimed to use two common genetic risk score (GRS) methods to construct prediction models for the efficacy of folic acid therapy on HHcy, and the best gene–environment prediction model was screened out. A prospective cohort study enrolling 638 HHcy patients was performed. We used a logistic regression model to estimate the associations of two GRS methods with the efficacy. Performances were compared using area under the receiver operating characteristic curve (AUC). The simple count genetic risk score (SC-GRS) and weighted genetic risk score (wGRS) were found to be independently associated with the efficacy of folic acid treatment for HHcy. Using the SC-GRS, per risk allele increased with a 1·46-fold increased failure risk (P < 0·001) after adjustment for traditional risk factors, including age, sex, BMI, smoking, alcohol consumption, history of diabetes, history of hypertension, history of hyperlipidaemia, history of stroke and history of CHD. When used the wGRS, the association was strengthened (OR = 2·08, P < 0·001). Addition of the SC-GRS and wGRS to the traditional risk model significantly improved the predictive ability by AUC (0·859). A precise gene–environment predictive model with good performance was developed for predicting the treatment failure rate of folic acid therapy for HHcy.

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Efficacy of Folic Acid Therapy in Patients with Hyperhomocysteinemia

Abstract: More than 40% patients with HHcy failed to reach the normal range (5-15 μmol/L) after 3 months of folic acid supplementation. Further prospective studies are warranted to explore the reasons for failure.

Cited by 23 publications

References 32 publications

CBS gene polymorphism and promoter methylation‐mediating effects on the efficacy of folate therapy in patients with hyperhomocysteinemia

CBS gene polymorphism and promoter methylation‐mediating effects on the efficacy of folate therapy in patients with hyperhomocysteinemia

Effect of Moxibustion on Hyperhomocysteinemia and Oxidative Stress Induced by High‐Methionine Diet

Prediction model for the efficacy of folic acid therapy on hyperhomocysteinaemia based on genetic risk score methods

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