IntroductionMigraine is a chronic neurovascular disorder that, in Western countries, affects approximately 15% of the general population [1]. The aetiology of migraine is still unknown but several studies support a strong genetic basis for the disease [2]. Mutations in the CACNA1A and ATP1A2 genes are associated with familial hemiplegic migraine, a rare subtype of migraine with aura [3,4]. The genes involved in the more common form of migraine, like migraine with and without aura, are still unknown.Epidemiological studies have shown the presence of a significant comorbidity between migraine and some diseases related to the HLA system, like asthma and narcolepsy [5,6]. This comorbidity suggests the presence, within the HLA region, of genetic factors involved in the disease pathogenesis.Previous studies evaluating the relation between HLA system and migraine provided conflicting results [7,8]. Recently, a significant association was found between migraine and polymorphisms of two genes, TNF-alpha and TNF-beta, located in the HLA Class III region [9,10].To further investigate this issue, we performed an association study between polymorphisms of the HLA-DRB1 gene and migraine in a large cohort of Italian migraine patients. The purpose of this study was to assess whether HLA-DRB1 alleles confer susceptibility to migraine or are related to specific clinical subgroups. -005-0180-3 Association between migraine and HLA-DRB1 gene polymorphisms Abstract 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.J Headache Pain (2005) 6:185-187 DOI 10.1007/s10194

This study is the first to demonstrate a role for an interaction between simultaneous variations of genes encoding for NOS and components of RAS in the progression of MGN. Interactions between various polymorphisms may explain conflicting results obtained in previous studies that examined single gene variations, since the effect of a single locus variation may be influenced by the simultaneous presence of other variant alleles in polygenic diseases such as primary GN. However, the small sample sizes and possible multiple interactions limited the interpretation of the current findings, which may represent true biological interaction or simply statistical interactions or spurious results due to the small sample sizes.