Homocysteine plasma levels in patients treated with antiepileptic drugs depend on folate and vitamin B12 serum levels, but not on genetic variants of homocysteine metabolism
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Alexander Semmler
, Susanna Moskau-Hartmann , Birgit Stoffel-Wagner , Christian Elger und Michael Linnebank
Abstract
Background: Antiepileptic drugs (AEDs) are commonly used in the treatment of epilepsy, psychiatric diseases and pain disorders. Several of these drugs influence blood levels of folate and vitamin B12 and, consequently, homocysteine. This may be relevant for AED effects and side effects. However, not only folate and vitamin B12, but also genetic variants modify homocysteine metabolism. Here, we aimed to determine whether there is a pharmacogenetic interaction between folate, vitamin B12 and genetic variants and homocysteine plasma level in AED-treated patients.
Methods: In this mono-center study, we measured homocysteine, folate and vitamin B12 plasma levels in a population of 498 AED-treated adult patients with epilepsy. In addition, we analyzed the genotypes of seven common genetic variants of homocysteine metabolism: methylenetetrahydrofolate reductase (MTHFR) c.677C>T and c.1298A>C, methionine synthase (MTR) c.2756A>G, dihydrofolate reductase (DHFR) c.594+59del19bp, cystathionine β-synthase (CBS) c.844_855ins68, transcobalamin 2 (TC2) c.776C>G and methionine synthase reductase (MTRR) c.66G>A.
Results: On multivariate logistic regression, folate and vitamin B12 levels, but none of the genetic variants, were predictive for homocysteine levels.
Conclusions: These data suggest that, in AED-treated patients, folate and vitamin B12 play important roles in the development of hyperhomocysteinemia, whereas genetic variants of homocysteine metabolism do not and thus do not contribute to the risk of developing hyperhomocysteinemia during AED treatment.
References
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©2013 by Walter de Gruyter Berlin Boston
Artikel in diesem Heft
- Masthead
- Masthead
- Editorial
- Special issue on advances and controversies in B vitamins and choline
- Reviews
- B-Vitamin dependent methionine metabolism and alcoholic liver disease
- Metabolic crosstalk between choline/1-carbon metabolism and energy homeostasis
- Proteomics of vitamin B12 processing
- Unexpected high plasma cobalamin/Proposal for a diagnostic strategy
- Clinical recognition and aspects of the cerebral folate deficiency syndromes
- Choline-containing phospholipids: relevance to brain functional pathways
- The ‘golden age’ of DNA methylation in neurodegenerative diseases
- Mechanisms of the beneficial effects of vitamin B6 and pyridoxal 5-phosphate on cardiac performance in ischemic heart disease
- The diagnostic utility of folate receptor autoantibodies in blood
- Red cell or serum folate: what to do in clinical practice?
- Formate: an essential metabolite, a biomarker, or more?
- The role of homocysteine in bone remodeling
- Mini Reviews
- Neuroprotective actions of perinatal choline nutrition
- Normal prions as a new target of cobalamin (vitamin B12) in rat central nervous system
- Molecular mechanisms underlying the potentially adverse effects of folate
- Betaine homocysteine methyltransferase (BHMT)-dependent remethylation pathway in human healthy and tumoral liver
- Hydrogen sulfide as an oxygen sensor
- Opinion Paper
- B vitamin therapy for homocysteine: renal function and vitamin B12 determine cardiovascular outcomes
- Research Articles
- One year B and D vitamins supplementation improves metabolic bone markers
- Effect of 1 year B and D vitamin supplementation on LINE-1 repetitive element methylation in older subjects
- Aqueous humor glycation marker and plasma homocysteine in macular degeneration
- Homocysteine plasma levels in patients treated with antiepileptic drugs depend on folate and vitamin B12 serum levels, but not on genetic variants of homocysteine metabolism
- Trends in clinical laboratory homocysteine testing from 1997 to 2010: the impact of evidence on clinical practice at a single institution
- Three family members with elevated plasma cobalamin, transcobalamin and soluble transcobalamin receptor (sCD320)
- Plasma choline and betaine correlate with serum folate, plasma S-adenosyl-methionine and S-adenosyl-homocysteine in healthy volunteers
- Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain
Artikel in diesem Heft
- Masthead
- Masthead
- Editorial
- Special issue on advances and controversies in B vitamins and choline
- Reviews
- B-Vitamin dependent methionine metabolism and alcoholic liver disease
- Metabolic crosstalk between choline/1-carbon metabolism and energy homeostasis
- Proteomics of vitamin B12 processing
- Unexpected high plasma cobalamin/Proposal for a diagnostic strategy
- Clinical recognition and aspects of the cerebral folate deficiency syndromes
- Choline-containing phospholipids: relevance to brain functional pathways
- The ‘golden age’ of DNA methylation in neurodegenerative diseases
- Mechanisms of the beneficial effects of vitamin B6 and pyridoxal 5-phosphate on cardiac performance in ischemic heart disease
- The diagnostic utility of folate receptor autoantibodies in blood
- Red cell or serum folate: what to do in clinical practice?
- Formate: an essential metabolite, a biomarker, or more?
- The role of homocysteine in bone remodeling
- Mini Reviews
- Neuroprotective actions of perinatal choline nutrition
- Normal prions as a new target of cobalamin (vitamin B12) in rat central nervous system
- Molecular mechanisms underlying the potentially adverse effects of folate
- Betaine homocysteine methyltransferase (BHMT)-dependent remethylation pathway in human healthy and tumoral liver
- Hydrogen sulfide as an oxygen sensor
- Opinion Paper
- B vitamin therapy for homocysteine: renal function and vitamin B12 determine cardiovascular outcomes
- Research Articles
- One year B and D vitamins supplementation improves metabolic bone markers
- Effect of 1 year B and D vitamin supplementation on LINE-1 repetitive element methylation in older subjects
- Aqueous humor glycation marker and plasma homocysteine in macular degeneration
- Homocysteine plasma levels in patients treated with antiepileptic drugs depend on folate and vitamin B12 serum levels, but not on genetic variants of homocysteine metabolism
- Trends in clinical laboratory homocysteine testing from 1997 to 2010: the impact of evidence on clinical practice at a single institution
- Three family members with elevated plasma cobalamin, transcobalamin and soluble transcobalamin receptor (sCD320)
- Plasma choline and betaine correlate with serum folate, plasma S-adenosyl-methionine and S-adenosyl-homocysteine in healthy volunteers
- Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain