The serotonin transporter gene polymorphism STin2 VNTR confers an increased risk of inconsistent response to triptans in migraine patients.
The aim of the present observational study was to assess the value of the C825T polymorphism of the beta-3 subunit of G proteins (GNB3) as well as of variants in the SLC6A4 gene (5HTTLPR and STin2 VNTR) and DRD2 gene (TaqI A and NcoI) as predictive markers for consistency in headache response to triptans in migraine patients. Consistent responders to triptans were defined as the migraineurs who experienced a > or =2 point reduction in a 4-point scale intensity of pain from 3 (severe) to 0 (absent) 2h after triptan administration, in at least two attacks out of the three. Genotyping was performed by PCR and PCR-RFLP on genomic DNA extracted from peripheral blood. The impact of clinical and biological variables on consistency status of headache response to triptans was evaluated by using a binary logistic regression model with stepwise selection. Forty-three (33%) of the 130 migraine patients included in the study did not consistently respond to triptan administration. In a binary logistic regression model, STin 2.12/12 genotype (OR=3.363, 95% CI: 1.262-8.966, P=0.005) and non-use of migraine prophylactic medications (OR=2.848, 95% CI: 1.019-7.959, P=0.010) were found as significant factors increasing the odds of achieving inconsistent response to triptans. The analysis of classificatory power of the model showed moderate values of sensitivity (0.56), high specificity (0.87), and an overall prediction correctness (0.77). These results support the role of STin2 VNTR polymorphism of serotonin transporter gene as a relevant genetic factor conferring a higher risk of inconsistent response to triptans in migraine patients.
Terrazzino
Salvatore
S
Università del Piemonte Orientale A. Avogadro, DiSCAFF and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica, Via Bovio 6, Novara, Italy.
Viana
Michele
M
Floriddia
Elisa
E
Monaco
Francesco
F
Mittino
Daniela
D
Sances
Grazia
G
Tassorelli
Cristina
C
Nappi
Giuseppe
G
Rinaldi
Maurizio
M
Canonico
Pier Luigi
PL
Genazzani
Armando A
AA
D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D007558:Italy; D016015:Logistic Models; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy* / Q000235:genetics; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014363:Tryptamines / Q000627:therapeutic use*; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
C454420:G-protein beta3 subunit; D017448:Receptors, Dopamine D2; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D014363:Tryptamines; D004247:DNA; D020962:Heterotrimeric GTP-Binding Proteins