Genetic Polymorphisms in Enzymes Involved in One-Carbon Metabolism and Anti-epileptic Drug Monotherapy on Homocysteine Metabolism in Patients With Epilepsy.
Genetic Polymorphisms in Enzymes Involved in One-Carbon Metabolism and Anti-epileptic Drug Monotherapy on Homocysteine Metabolism in Patients With Epilepsy.
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一碳代谢酶基因多态性及抗癫痫药物单药治疗对癫痫患者同型半胱氨酸代谢的影响
DOI：
10.3389/fneur.2021.683275
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发表时间：
2021
影响因子：
3.4
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Zhu S;Ni G;Sui L;Zhao Y;Zhang X;Dai Q;Chen A;Lin W;Li Y;Huang M;Zhou L
目的：目的探讨一碳代谢（OCM）相关酶基因单核苷酸多态性（SNPs）和抗癫痫药物（AED）单药治疗对癫痫患者同型半胱氨酸（Hcy）代谢的影响，进一步探讨可能增加患者对AED影响Hcy失衡易感性的特异性SNPs。方法：该病例对照研究分析了279例癫痫患者，包括接受丙戊酸盐（VPA）（n = 53）、奥卡西平（OXC）（n = 71）、拉莫三嗪（LTG）（n = 55）或左乙拉西坦（LEV）（n = 35）单药治疗的患者和至少6个月未使用任何AED的患者（对照，n = 65）。检测患者血清维生素B12（vit B12）、叶酸（FA）和同型半胱氨酸（Hcy）水平，并对13个OCM相关酶基因的23个SNPs进行基因分型。结果如下：亚甲基四氢叶酸还原酶（MTHFR）rs 1801133与癫痫患者血清Hcy水平升高相关（P < 0.001），TT基因型患者的血清Hcy水平高于CC（P < 0.001）或CT（P < 0.001）基因型患者。随后的多元线性回归分析显示，AED单药治疗与VPA（与对照组相比：P = 0.023）或OXC（与对照组相比：P = 0.041），MTHFR rs 1801133 TT基因型（与CC：P < 0.001;与CT：P < 0.001），转钴胺素2（TCN 2）rs 1801198 CC（vs. GC：P = 0.039）和叶酸受体1（FOLR 1）rs 2071010 AA（vs. GA：P = 0.031）是高Hcy水平的独立危险因素。在OXC患者的亚组分析中，我们发现MTHFR rs 1801133 TT（vs. CC：P = 0.001; vs. CT：P < 0.001）和TCN 2 rs 1801198 CC（vs. GC：P = 0.021; vs. GG：P = 0.018）基因型患者的血清Hcy水平较高。结论：VPA、OXC和MTHFR rs 1801133 TT、TCN 2 rs 1801198 CC和FOLR 1 rs 2071010 AA基因型均为癫痫患者Hcy水平升高的独立危险因素。此外，MTHFR rs 1801133 TT和TCN 2 rs 1801198 CC的基因型可能增加患者对OXC破坏Hcy稳态的作用的易感性。
Aims: To investigate the effects of single nucleotide polymorphisms (SNPs) in genes of one-carbon metabolism (OCM) related enzymes and anti-epileptic drug (AED) monotherapy on homocysteine (Hcy) metabolism in patients with epilepsy, and to further explore specific SNPs that may increase patients' susceptibility to the effects of AEDs on the Hcy imbalance. Method: This case-control study analyzed 279 patients with epilepsy, including patients receiving monotherapy with valproate (VPA) (n = 53), oxcarbazepine (OXC) (n = 71), lamotrigine (LTG) (n = 55), or levetiracetam (LEV) (n = 35) and patients who had not taken any AEDs (controls, n = 65) for at least 6 months. Serum levels of vitamin B12 (vit B12), folate (FA) and Hcy were measured, and 23 SNPs in 13 genes of OCM-related enzymes were genotyped in all patients. Results: Methylenetetrahydrofolate reductase (MTHFR) rs1801133 was associated with elevated serum Hcy levels in patients with epilepsy (P < 0.001), and patients presenting the TT genotype exhibited higher serum Hcy levels than patients with the CC (P < 0.001) or CT (P < 0.001) genotype. A subsequent multiple linear regression analysis showed that AED monotherapy with VPA (vs. control: P = 0.023) or OXC (vs. control: P = 0.041), and genotypes of MTHFR rs1801133 TT (vs. CC: P < 0.001; vs. CT: P < 0.001), transcobalamin 2 (TCN2) rs1801198 CC (vs. GC: P = 0.039) and folate receptor 1 (FOLR1) rs2071010 AA (vs. GA: P = 0.031) were independent risk factors for higher Hcy levels. In the subgroup analysis of patients taking OXC, we found that patients with genotypes of MTHFR rs1801133 TT (vs. CC: P = 0.001; vs. CT: P < 0.001) and TCN2 rs1801198 CC (vs. GC: P = 0.021; vs. GG: P = 0.018) exhibited higher serum Hcy levels. Conclusions: VPA, OXC, and genotypes of MTHFR rs1801133 TT, TCN2 rs1801198 CC, and FOLR1 rs2071010 AA are all independent risk factors for elevated Hcy levels in patients with epilepsy. Moreover, genotypes of MTHFR rs1801133 TT and TCN2 rs1801198 CC may increase patients' susceptibility to the effect of OXC on disrupting Hcy homeostasis.
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影响因子：
5
作者：
Bharatkumar, Venkata Pinnelli;Rudreshkumar, Kondapura Jayadevappa;Christopher, Rita
通讯作者：
Christopher, Rita
影响因子：
6.2
作者：
Dhonukshe-Rutten, RAM;Pluijm, SMF;van Staveren, W
通讯作者：
van Staveren, W
影响因子：
3.6
作者：
Chango, A;Boisson, F;Nicolas, JP
通讯作者：
Nicolas, JP
影响因子：
3.2
作者：
Kurosawa, Yuko;Furugen, Ayako;Iseki, Ken
通讯作者：
Iseki, Ken
影响因子：
3
作者：
Emeksiz, Hamdi Cihan;Serdaroglu, Ayse;Hasanoglu, Alev
通讯作者：
Hasanoglu, Alev