Premium
Association Study of MTHFD 1 Coding Polymorphisms R 134 K and R 653 Q With Migraine Susceptibility
Author(s) -
Sutherland Heidi G.,
Hermile Heloise,
Sanche Rebecca,
Me Saras,
Lea Rod A.,
Haupt Larisa M.,
Griffiths Lyn R.
Publication year - 2014
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/head.12428
Subject(s) - migraine , methylenetetrahydrofolate reductase , single nucleotide polymorphism , homocysteine , genotype , allele , genetics , medicine , biology , gene
Objective There is evidence that folate metabolism has a role in migraine pathophysiology, particularly in the migraine with aura (MA) subtype. In this study, we investigate whether two non‐synonymous single nucleotide polymorphisms ( SNP s), rs1950902 ( C 401T; R 134 K ) and rs2236225 ( G 1958 A ; R 653 Q ), in MTHF dehydrogenase ( MTHFD 1) are associated with migraine in an A ustralian case‐control population. Background Increased plasma levels of homocysteine, one of the metabolites produced in the folate pathway, has been found to be a risk factor for migraine. There is also a genetic link: a common polymorphism (rs1801133, C 667 T ) that reduces the catalytic activity of the enzyme that catalyzes the formation of homocysteine, methylenetetrahydrofolate reductase ( MTHFR ), is associated with an increase in risk of MA . MTHFD 1 is a crucial multifunctional enzyme that catalyzes three separate reactions of the folate pathway and therefore variants in MTHFD 1 may also influence migraine susceptibility. Methods The R 134 K and R 653 Q variants in MTHFD 1 were genotyped in an A ustralian cohort of 520 unrelated migraineurs (162 were diagnosed with migraine without aura [ MO ] and 358 with MA ) and 520 matched controls. Data were analyzed for association with migraine and for interaction with the MTHFR C 667 T polymorphism. Results We find no significant differences in genotype or allele frequencies for either SNP between migraineurs and controls, or when either MO or MA cases were compared with controls. In addition, these MTHFD 1 polymorphisms did not appear to influence the risk of MA conferred by the MTHFR 667 T allele. Conclusions We find no evidence for association of the MTHFD 1 R 134 K and R 653 Q polymorphisms with migraine in our A ustralian case‐control population. However, as folate metabolism appears to be important in migraine, particularly with respect to the aura component, future studies using high throughput methods to expand the number of SNP s in folate‐related genes genotyped and investigation of interactions between SNP s may be justified.