Frequencies of genetic polymorphisms related to triptans metabolism in chronic migraine.
Chronic migraine (CM) prevalence ranges around 1-5%. Most of these patients usually treat their acute attacks with triptans, whose efficacy is extremely variable. A genetic basis for migraine is evident and many susceptibility genes have been described, as well as gene polymorphisms possibly implied in therapy response. Several factors could be involved in the evolution of episodic migraine into a chronic form, such as natural history, psychiatric comorbidity, and the individual's response to therapy. During a study aimed at detecting connections between genotype and response to triptans administration, we characterized a CM population for polymorphisms in the genes coding for monoamine oxidase A, g-protein beta 3 and the cytochromes CYP3A4 and CYP1A2. Alleles and genotypes distributions were compared with known frequencies of healthy Caucasian populations. A significant association with CM was found for the long allele of monoamine oxidase A 30 bp VNTR and CYP1A2*1F variant. Such genomic analysis is part of an integrated platform able to evaluate different levels of metabolic pathways of drugs in CM and their influence in the chronicization process.
Gentile
Giovanna
G
Department of Biochemical Sciences, Advanced Molecular Diagnostic Unit, 2nd School of Medicine, Sapienza University, Sant'Andrea Hospital, Via di Grottarossa 1035, Rome, Italy.
Missori
Serena
S
Borro
Marina
M
Sebastianelli
Alisa
A
Simmaco
Maurizio
M
Martelletti
Paolo
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004252:DNA Mutational Analysis; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics*; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008995:Monoamine Oxidase / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D014363:Tryptamines / Q000378:metabolism*
C454420:G-protein beta3 subunit; D005819:Genetic Markers; D014363:Tryptamines; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D008995:Monoamine Oxidase; D020962:Heterotrimeric GTP-Binding Proteins