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Genetic variants of homocysteine metabolism and multiple sclerosis: a case-control study


Ineichen, Benjamin V; Keskitalo, Salla; Farkas, Melinda; Bain, Nadja; Kallweit, Ulf; Weller, Michael; Klotz, Luisa; Linnebank, Michael (2014). Genetic variants of homocysteine metabolism and multiple sclerosis: a case-control study. Neuroscience Letters, 562:75-78.

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is necessary for the synthesis of methionine and S-adenosylmethionine, which is necessary for CNS (re-)myelination. The MTHFR variant c.1298A>C was associated with the development of relapsing remitting multiple sclerosis (RRMS) in a German population. This study aimed at analyzing whether further genetic variants of methionine metabolism are associated with the development or the clinical course of RRMS. Therefore, genomic DNA of 147 serial German RRMS patients and 147 matched healthy controls was genotyped for five polymorphic variants of methionine metabolism. Statistical analyses were performed using multivariate binary and linear regression analyses. We show that the insertion allele of cystathionine beta-synthase (CBS) c.844_855ins68bp and the G-allele of reduced folate carrier 1 (RFC1) c.80G>A were associated with an earlier age of onset of MS, suggesting gene-dose effects (median age of onset in years: 25-26-32; standardized regression coefficient beta: 0.216; p=0.030, and 29-31-35 years; beta: 0.282; p=0.005, respectively). Conclusively, mutant variants of CBS and RFC1 may be associated with the age of RRMS onset. Since methionine metabolism can be manipulated by supplementation of vitamins and amino acids, our data provide a rationale for novel ideas of preventive and therapeutic strategies in RRMS.

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is necessary for the synthesis of methionine and S-adenosylmethionine, which is necessary for CNS (re-)myelination. The MTHFR variant c.1298A>C was associated with the development of relapsing remitting multiple sclerosis (RRMS) in a German population. This study aimed at analyzing whether further genetic variants of methionine metabolism are associated with the development or the clinical course of RRMS. Therefore, genomic DNA of 147 serial German RRMS patients and 147 matched healthy controls was genotyped for five polymorphic variants of methionine metabolism. Statistical analyses were performed using multivariate binary and linear regression analyses. We show that the insertion allele of cystathionine beta-synthase (CBS) c.844_855ins68bp and the G-allele of reduced folate carrier 1 (RFC1) c.80G>A were associated with an earlier age of onset of MS, suggesting gene-dose effects (median age of onset in years: 25-26-32; standardized regression coefficient beta: 0.216; p=0.030, and 29-31-35 years; beta: 0.282; p=0.005, respectively). Conclusively, mutant variants of CBS and RFC1 may be associated with the age of RRMS onset. Since methionine metabolism can be manipulated by supplementation of vitamins and amino acids, our data provide a rationale for novel ideas of preventive and therapeutic strategies in RRMS.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:6 March 2014
Deposited On:09 Oct 2014 12:58
Last Modified:05 Apr 2016 18:24
Publisher:Elsevier
ISSN:0304-3940
Publisher DOI:https://doi.org/10.1016/j.neulet.2014.01.008
PubMed ID:24412677

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