Cytochrome P450 2D6 and glutathione S-transferase M1 genotypes and migraine.
BACKGROUND
Migraine is thought to be a disease of the brain and trigeminovascular system. Migraine patients often claim that stress, food, and beverages trigger their attacks. Chemical substances in these foodstuffs with the property of triggering migraine attacks have not yet been characterised. Cytochrome P450 2D6 (CYP2D6) and glutathione S-transferase M1 (GSTM1) are thought to be present in the brain. They metabolise numerous environmental compounds. The genes exhibit genetic polymorphism that is associated with altered enzyme activity. The aim of this study was to determine if the genotypes of these two enzymes are associated with migraine.


METHODS
The study included 100 female patients and 245 female controls from the general population. Genomic DNA was isolated from whole blood. Allele specific PCR methods were used to identify the normal CYP2D6*1 allele and the mutated CYP2D6*3 and CYP2D6*4 alleles. Initially all samples were genotyped only for GSTM1 plus (+) and GSTM1 null (-) variants. All samples positive for GSTM1 were further analysed for the presence of allelic variants GSTM1*A and GSTM1*B.


RESULTS
None of the CYP2D6 and GSTM1 genotypes was associated with migraine. We observed an odds ratio (OR) for the poor metaboliser genotype of CYP2D6 of 1.4 (95% CI = 0.5-3.6) and for the GSTM1 null genotype of 1.0 (95% CI = 0.6-1.5).


CONCLUSIONS
The results of this study indicate that deficient metabolism because of mutated CYP2D6 alleles or GSTM1 allele variants is not important in the aetiology of migraine.
Mattsson
P
P
University Hospital, Uppsala, Sweden. Peter.Mattsson@neurologi.uu.se
Bjelfman
C
C
Lundberg
P O
PO
Rane
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004247:DNA / Q000097:blood; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008875:Middle Aged; D008881:Migraine Disorders / Q000201:enzymology* / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012016:Reference Values
D007527:Isoenzymes; D004247:DNA; D019389:Cytochrome P-450 CYP2D6; D005982:Glutathione Transferase