Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation

Menon, Saras, Lea, Rod A., Roy, Bishakha, Hanna, Michelle, Wee, Shirley, Haupt, Larisa M., Oliver, Chris, & Griffiths, Lyn R. (2012) Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation. Pharmacogenetics and Genomics, 22(10), pp. 741-749.

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Abstract

BACKGROUND: Migraine is a chronic disabling neurovascular condition that may in part be caused by endothelial and cerebrovascular disruption induced by hyperhomocysteinaemia. We have previously provided evidence indicating that reduction of homocysteine by vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the genotypic effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene variants on the occurrence of migraine in response to vitamin supplementation.

METHODS: This was a 6-month randomized, double-blinded placebo-controlled trial of daily vitamin B supplementation (B(6), B(9) and B(12)) on reduction of homocysteine and of the occurrence of migraine in 206 female patients diagnosed with migraine with aura.

RESULTS: Vitamin supplementation significantly reduced homocysteine levels (P<0.001), severity of headache in migraine (P=0.017) and high migraine disability (P=0.022) in migraineurs compared with the placebo effect (P>0.1). When the vitamin-treated group was stratified by genotype, the C allele carriers of the MTHFR C677T variant showed a higher reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.01) and percentage of high migraine disability (P=0.009) compared with those with the TT genotypes. Similarly, the A allele carriers of the MTRR A66G variants showed a higher level of reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.002) and percentage of high migraine disability (P=0.006) compared with those with the GG genotypes. Genotypic analysis for both genes combined indicated that the treatment effect modification of the MTRR variant was independent of the MTHFR variant.

CONCLUSION: This provided further evidence that vitamin supplementation is effective in reducing migraine and also that both MTHFR and MTRR gene variants are acting independently to influence treatment response in female migraineurs.

Impact and interest:

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18 citations in Web of Science®
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ID Code: 62499
Item Type: Journal Article
Refereed: Yes
Additional Information: Menon, Saras
Lea, Rod A
Roy, Bishakha
Hanna, Michelle
Wee, Shirley
Haupt, Larisa M
Oliver, Chris
Griffiths, Lyn R
eng
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
2012/08/29 06:00
Pharmacogenet Genomics. 2012 Oct;22(10):741-9. doi: 10.1097/FPC.0b013e3283576b6b.
Additional URLs:
Keywords: adolescent, adult, alleles, dietary supplements, double-blind method, female, Ferredoxin-NADP Reductase/*genetics, Folic Acid/administration & dosage, *genotype, humans, Methylenetetrahydrofolate Reductase (NADPH2)/*genetics, middle aged, Migraine with Aura/*drug therapy/enzymology/genetics, placebo effect, Vitamin B 12/administration & dosage, Vitamin B 6/administration & dosage, Vitamins/*administration & dosage, young adult
DOI: 10.1097/FPC.0b013e3283576b6b
ISSN: 1744-6872
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Lippincott Williams & Wilkins
Deposited On: 13 Sep 2013 02:02
Last Modified: 27 Jun 2017 08:49

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