1Department of Epidemiology,School of Public Health,Zhengzhou University,Zhengzhou 450001,Henan,People's Republic of China.
2Department of Biostatistics and Bioinformatics,School of Public Health and Tropical Medicine,Tulane University,New Orleans,LA 70112,USA.
Br J Nutr. 2018 Apr;119(8):887-895. doi: 10.1017/S0007114518000508.
The aim of this study is to analyse the efficacy rate of folate for the treatment of hyperhomocysteinaemia (HHcy) and to explore how folate metabolism-related gene polymorphisms change its efficacy. This study also explored the effects of gene-gene and gene-environment interactions on the efficacy of folate. A prospective cohort study enrolling HHcy patients was performed. The subjects were treated with oral folate (5 mg/d) for 90 d. We analysed the efficacy rate of folate for the treatment of HHcy by measuring homocysteine (Hcy) levels after treatment. Unconditioned logistic regression was conducted to analyse the association between SNP and the efficacy of folic acid therapy for HHcy. The efficacy rate of folate therapy for HHcy was 56·41 %. The MTHFR rs1801133 CT genotype, TT genotype and T allele; the MTHFR rs1801131 AC genotype, CC genotype and C allele; the MTRR rs1801394 GA genotype, GG genotype and G allele; and the MTRR rs162036 AG genotype and AG+GG genotypes were associated with the efficacy of folic acid therapy for HHcy (P<0·05). No association was seen between other SNP and the efficacy of folic acid. The optimal model of gene-gene interactions was a two-factor interaction model including rs1801133 and rs1801394. The optimal model of gene-environment interaction was a three-factor interaction model including history of hypertension, history of CHD and rs1801133. Folate supplementation can effectively decrease Hcy level. However, almost half of HHcy patients failed to reach the normal range. The efficacy of folate therapy may be genetically regulated.
本研究旨在分析叶酸治疗高同型半胱氨酸血症（HHcy）的疗效，并探讨叶酸代谢相关基因多态性如何改变其疗效。本研究还探讨了基因-基因和基因-环境相互作用对叶酸疗效的影响。进行了一项前瞻性队列研究，纳入了 HHcy 患者。这些患者接受口服叶酸（5mg/d）治疗 90d。我们通过治疗后测量同型半胱氨酸（Hcy）水平来分析叶酸治疗 HHcy 的疗效率。采用非条件逻辑回归分析 SNP 与叶酸治疗 HHcy 疗效的相关性。叶酸治疗 HHcy 的疗效率为 56.41%。MTHFR rs1801133 CT 基因型、TT 基因型和 T 等位基因；MTHFR rs1801131 AC 基因型、CC 基因型和 C 等位基因；MTRR rs1801394 GA 基因型、GG 基因型和 G 等位基因；以及 MTRR rs162036 AG 基因型和 AG+GG 基因型均与叶酸治疗 HHcy 的疗效相关（P<0.05）。其他 SNP 与叶酸疗效之间未见关联。基因-基因相互作用的最佳模型是包括 rs1801133 和 rs1801394 的两因素相互作用模型。基因-环境相互作用的最佳模型是包括高血压史、CHD 史和 rs1801133 的三因素相互作用模型。叶酸补充可以有效降低 Hcy 水平。然而，几乎一半的 HHcy 患者未能达到正常范围。叶酸治疗的疗效可能受到遗传调控。
