C Rivoiro

A polymorphism of the hypocretin receptor 2 gene is associated with cluster headache

Several polymorphisms of the hypocretin/orexin system genes were evaluated in 109 cluster headache patients and 211 controls. The 1246 G>A polymorphism of the gene was significantly different between cases and controls. Homozygosity for the G allele was associated with an increased disease risk (OR: 6.79, 95% CI, 2.25 to 22.99). The data suggest that the HCRTR2 gene or a linked locus significantly modulates the risk for cluster headache.

A Polymorphism in the Interleukin-1α Gene Influences the Clinical Features of Migraine

Objective.—To evaluate whether a particular genotype of the interleukin‐1α (IL1A) gene affects the clinical features of migraine.

Lack of association between the 3092 T→C Clock gene polymorphism and cluster headache

Recent studies suggested that genetic factors play a role in cluster headache (CH). However, the type and the number of genes involved in the disease are still unclear. We performed an association study in a cohort of Italian CH patients to evaluate whether a particular allele or genotype of the Clock gene would modify the occurrence and the clinical features of the disease. One hundred and seven CH patients, diagnosed according to the International Classification of Headache Disorders, 2nd Edition, (ICHD-II) criteria, and 210 healthy age, sex and ethnicity-matched controls were genotyped for the 3092 T°C Clock gene polymorphism (also known as 3111 T°C). Phenotype and allele frequencies were similarly distributed in CH patients and controls. The clinical features of the disease were not significantly influenced by different genotypes. In conclusion, our study suggests that the 3092 T°C polymorphism of the Clock gene is unlikely to play an important role in cluster headache.

Association between migraine and HLA–DRB1 gene polymorphisms

We examined the distribution of HLA–DRB1 alleles in a cohort of 255 Italian migraine patients and in a control group of 325 healthy subjects. The frequency of DRB1*12 allele was found to be significantly reduced (p=0.02) in patients with migraine while the DRB1*16 allele was significantly increased (p=0.04) in comparison with controls. When the patients were divided into disease subgroups (migraine with and without aura), HLA–DRB1**16 allele was significantly increased (p<0.05) only in migraine without aura patients. We conclude that, in Italian patients, migraine is associated with different alleles of the HLA–DRB1 locus. Our data suggest the presence of a genetic susceptibility factor for migraine within the HLA region.

Absence of linkage between the interleukin-6 gene (−174 G/C) polymorphism and migraine

To assess the role of interleukin-6 (IL-6) in migraine, we analyzed the -174 G/C IL-6 gene polymorphism in 268 patients with migraine and 305 controls. No significant difference in the distribution of IL-6 genotypes (chi(2)=0.601, P=0.74) and allelic frequencies (chi(2)=0.024, P=0.876) was found. When patients were subdivided into subgroups (migraine with aura, migraine without aura and mixed headaches), IL-6 alleles were similarly distributed. Comparison of the clinical features of the disease with the -174 G/C IL-6 genotypes showed no significant difference. In conclusion, we found no significant association between the -174 G/C IL-6 polymorphism and the occurrence or the clinical features of migraine.

Apolipoprotein E gene polymorphisms in patients with migraine

To investigate the role of apolipoprotein E (APOE) polymorphisms in migraine, we analyzed the APOE genotypes of 241 migraine patients and 587 controls. The results of a Chi-square analysis indicated that APOE alleles were similarly distributed (chi(2)=2.89, P=0.24) between cases and controls. However, we found a significant (P<0.001) increase of the varepsilon2-varepsilon4 genotype in the group of migraine patients. Patients were divided into three subgroups: migraine with aura; migraine without aura; and mixed headaches (migraine associated with tension-type headache). Subgroup analysis showed that the varepsilon2-varepsilon4 genotype was significantly increased only in patients with mixed headaches. The stratification of patients by APOE status did not reveal significant associations with the clinical features of the disease. In conclusion, we observed no significant association between APOE polymorphisms and migraine. The association between the APOE varepsilon2-varepsilon4 genotype and the tension-type headache deserves further evaluation.

The therapy of multiple sclerosis with immune-modulating or immunosuppressive drug. A critical evaluation based upon evidence based parameters and published systematic reviews.

Today many different drugs are available for treatment of multiple sclerosis (MS). Interferons, glatiramer acetate, mitoxantrone, and natalizumab have been approved by the regulatory authorities of many countries for the treatment of MS. Evidence based medicine (EBM) principles allow physicians to better address the correct treatment for patients. This article aimed to review all the clinical trials on immune-modulating and immunosuppressive drugs on the basis of the EBM principles. Based on the evidence to date interferon beta represents the best therapeutic option, particularly if given at high doses and with multiple injections per week. Due to its lower efficacy, glatiramer acetate should be used as a second choice in case of intolerable side effects or toxicity of interferon beta. Great efficacy has been demonstrated for mitoxantrone and natalizumab. These drugs should be, however, used with particular attention for their potential toxic effects.

Genetics of cluster headache: an update

Up to a few years ago, cluster headache (CH) was not thought to be an inherited disorder. However, several recent studies have suggested that genetic factors play a role in the disease. Genetic epidemiological surveys have shown that first–degree relatives of CH patients are more likely to have CH than the general population. CH has been reported in some concordant monozygotic twin pairs. At present, the type and the number of genes involved in the disease are still unclear. No mutation in the CACNA1A and NOS genes was found in CH patients. Recently, we have reported a significant association between the HCRTR2 gene and the disease. The purpose of this review is to describe recent advances in the genetics of CH.

The 1246G-->A polymorphism of the HCRTR2 gene is not associated with migraine.

Studies in experimental animals have suggested that the hypocretin/orexin system may be involved in migraine pathophysiology. Using a case-control design study, we genotyped 246 migraine patients and 239 healthy controls for the 1246G→A polymorphism of the hypocretin receptor 2 (HCRTR2) gene. Genotypic and allelic frequencies of the examined polymorphism were similarly distributed between cases and controls (χ2 = 2.22, P = 0.14 and χ2 = 2.45, P = 0.29, respectively). When different migraine subgroups were compared (migraine with aura vs. migraine without aura and episodic vs. chronic migraine) no significant difference was found. Comparison of the clinical features of the disease with the 1246G→A genotypes showed no significant difference. Our data suggest that the HCRTR2 gene is not a genetic risk factor in migraine.

HLA-DRB1 genotyping in Italian migraine patients

We examined the distribution of HLA-DRB1 alleles in a cohort 255 Italian migraine patients and in a control group of 325 healthy subjects. 214 patients fulfilled the ICHD-II criteria for migraine without aura and 41 patients the criteria for migraine with aura. The frequency of DRB1*16 allele was found to be significantly increased in migraine without aura patients (p=0.02; OR 1.97, 95% CI: 1.10-3.54) than in healthy controls. The frequencies of HLA-DRB1 alleles were not significantly different between migraine with aura patients and controls. We did not detect any effect of DRB1 alleles on age at onset, duration of the disease, frequency and duration of migraine attacks. Our data suggest the presence of a genetic susceptibility factor for migraine without aura within the HLA region.