CBS gene polymorphism and promoter methylation‐mediating effects on the efficacy of folate therapy in patients with hyperhomocysteinemia
| Autor: | Qinglin Zhao, Opolot Godfrey, Limin Yue, Xiaowen Huang, Binghui Du, Bingnan Ren, Weidong Zhang, Dankang Li, Chengda Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Hyperhomocysteinemia Genotype Pharmacogenomic Variants Cystathionine beta-Synthase Polymorphism Single Nucleotide 03 medical and health sciences Folic Acid 0302 clinical medicine Gene Frequency Internal medicine Drug Discovery Odds Ratio Genetics Humans Medicine Promoter Regions Genetic Molecular Biology Alleles Genetics (clinical) Aged Polymorphism Genetic biology business.industry Methylation Odds ratio DNA Methylation Middle Aged medicine.disease Cystathionine beta synthase Treatment Outcome 030104 developmental biology Endocrinology Pharmacogenetics 030220 oncology & carcinogenesis DNA methylation biology.protein Molecular Medicine Female Gene polymorphism business Biomarkers |
| Zdroj: | The Journal of Gene Medicine. 22 |
| ISSN: | 1521-2254 1099-498X |
| DOI: | 10.1002/jgm.3156 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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