Family-based association analysis of functional VNTR polymorphisms in the dopamine transporter gene in migraine with and without aura.

Because of the role of dopamine in triggering migraine attacks, genes of the dopamine system are candidates for involvement in migraine. We examined three VNTR polymorphisms in the dopamine transporter, the 5'UTR VNTR, the intron 8 VNTR and the intron 14 VNTR, in a sample of 205 family trios. We used the transmission disequilibirium test (TDT) to examine the transmission of these three markers and their haplotypes to offspring affected by migraine. We found no significant transmission distortion of any marker. Likewise haplotypes of the three markers did not show significant overall or individual association with migraine. Finally we examined migraine with and without aura, and likewise found no association between dopamine transporter VNTRs or their haplotypes and either classification of the disease. We conclude that functional genetic variation in the dopamine transporter does not act as a significant risk factor for migraine.

Family-based analysis of serotonin transporter gene polymorphisms in migraine with and without aura.

Genetic epidemiological twin studies have demonstrated a significant heritability for migraine, with > 60% of liability to migraine either with or without aura coming from additive genetic factors. Because of the essential role of serotonin in the pathophysiology and treatment of migraine, genes of the serotonin system are candidates for involvement in migraine. Consequently, we examined two functional VNTR polymorphisms in the serotonin transporter gene, the 5-HTTLPR and the intron 2 VNTR, in a sample of 212 family trios each with a proband with childhood migraine, 153 with migraine without aura (MoA) and 59 with migraine with aura (MA). For the first time, we used transmission disequilibrium test analysis with the program TDTPHASE to examine the transmission of these two markers and their haplotypes to offspring affected by migraine. We found no significant transmission distortion of any marker, with the common L allele of the 5-HTTLPR transmitted 170 times and not transmitted 178 times, and the S allele 130 vs. 122 times. Likewise, the common 12 allele of the intron 2 VNTR was transmitted 201 times and not transmitted 188 times, and the 10 allele 107 vs. 120 times. The markers were not associated with MoA and MA and none of the haplotypes was associated with overall migraine, MoA or MA. The 5-HTTLPR and the intron 2 VNTRs do not play a major role in susceptibility to migraine.

Clinical features, classification and prognosis of migraine and tension-type headache in children and adolescents: a long-term follow-up study.

We performed a long-term follow-up examination in children and adolescents with migraine and tension-type headache (TTH) in order to investigate the evolution of clinical features and headache diagnoses, to compare International Classification of Headache Disorders (ICHD)-I and ICHD-II criteria and to identify prognostic factors. We re-examined 227 patients (52.4% female, age 17.6 +/- 3.1 years) 6.6 +/- 1.6 years after their first presentation to a headache centre using identical semistructured questionnaires. Of 140 patients initially diagnosed with migraine, 25.7% were headache free, 48.6% still had migraine and 25.7% had TTH at follow-up. Of 87 patients with TTH, 37.9% were headache free, 41.4% still had TTH and 20.7% had migraine. The number of subjects with definite migraine was higher in ICHD-II than in ICHD-I at baseline and at follow-up. The likelihood of a decrease in headache frequency decreased with a changing headache location at baseline (P < 0.0001), with the time between baseline and follow-up (P = 0.0019), and with an initial diagnosis of migraine (P = 0.014). Female gender and a longer time between headache onset and first examination tended to have an unfavourable impact. In conclusion, 30% of the children and adolescents presenting to a headache centre because of migraine or TTH become headache-free in the long-term. Another 20-25% shift from migraine to TTH or vice versa. ICHD-II criteria are superior to those of ICHD-I in identifying definite migraine in children and adolescents presenting to a headache centre. The prognosis is adversely affected by an initial diagnosis of migraine and by changing headache location, and it tends to be affected by an increasing time between headache onset and first presentation.