Chromosome 6p-encoded HLA-DR2 determinant discriminates migraine without aura from migraine with aura

Martelletti, Paolo; Lulli, Patrizia; Morellini, M; Mariani, Bruno; Pennesi, Giuseppina; Cappellacci, Sandra; Brioli, Gloria; Giacovazzo, M; Trabace, S

doi:10.1016/s0198-8859(98)00087-1

Cited by 26 publications

(25 citation statements)

References 33 publications

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“…Furthermore, it has been found that the less common -308A allele is strongly associated with the MHC haplotype HLA-A1, B8, DR3, which is, in turn, associated with high TNF production [10]. Martelletti et al [17] reported that the low producing HLA class II DR2 antigen is decreased in MA relative to both MO and controls. This supports our finding that -308A allele is associated with MA but not with MO.…”

Section: Discussionmentioning

confidence: 99%

Investigation of TNFA 308G > A and TNFB 252G > A polymorphisms in genetic susceptibility to migraine

et al. 2009

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We aimed to look for the association of tumor necrosis factor (TNF) gene polymorphisms (TNFA 308G > A, and TNFB 252G > A) in genetic susceptibility to migraine. The pathogenesis of migraine involves many immune-mediated mechanisms in the vascular endothelium. TNF, being a potent immunomodulator and pro-inflammatory cytokine, is suggested to be involved in inflammatory reactions leading to migraine attacks. A total of 216 normotensive migraine patients, 160 tension type headache (TTH) patients and 216 healthy controls (HC) were recruited in the study. The genetic polymorphisms were investigated through SNP association analysis using a matched case control migraine population. Genotyping of TNFA 308G > A polymorphism and TNFB 252G > A was done using ARMS PCR and PCR-RFLP, respectively. A borderline association was observed in TNFA 308GA genotype in migraine patients versus HC (p = 0.043; OR = 1.763; 95% CI = 1.019-3.051). After sub-grouping migraine into migraine with aura (MA) or without aura, significant difference at genotypic (p = 0.015; OR = 2.293; 95% CI = 1.172-4.487) as well as allelic (p = 0.035; OR = 1.955; 95% CI = 1.047-3.651) level was evident. The difference was even more significant in female MA at genotypic (p = 0.006; OR = 2.901; 95% CI = 1.361-6.181) and allelic level (p = 0.017; OR = 2.318; 95% CI = 1.159-4.635) as well as for A allele carriers in MA [p value = 0.020; OR = 2.205 (1.132-4.295)] and female MA (p value = 0.008; OR = 2.741; CI = 1.297-5.792). No association of TNFB252G > A was observed in migraine patients or any subgroups. We did not find any association of TNFA or TNFB gene polymorphisms with TTH. In conclusion, the TNFA 308G > A polymorphism was found to be associated with MA, particularly in females, whereas we could not find any association of TNFB 252G > A polymorphism in genetic susceptibility to migraine on comparing the migraine patients with HC or TTH patients.

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Section: Discussionmentioning

confidence: 99%

Investigation of TNFA 308G > A and TNFB 252G > A polymorphisms in genetic susceptibility to migraine

et al. 2009

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“…Trabace et al [67] found that the frequency of TNFB*2 allele, located in the HLA class III region, was significantly increased and that of TNFB1 decreased in MO, suggesting that the TNFB*2 allele confers a high risk for MO. The same group had previously observed a protective role for the HLA-DR2 antigen in MA [68]. Finally, a polymorphism in the interleukin-1alpha gene was found to influence age at onset of migraine and was associated with MA [69].…”

Section: Migraine and Genes Involved In Inflammationmentioning

confidence: 67%

The “typical” migraines: genetic studies and some practical considerations

2003

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"Typical" migraine as a complex disease: genetic epidemiology, twin and segregation analysis studies That migraine runs in families is an ancient observation. Familiarity however is not synonymous with heritability, especially given the wide prevalence of migraine and the possibility that familial occurrence is due to chance. In order to assess the heritability of migraine, e.g. the rate of variance attributable to genetic factors, the disease risk of relatives of migraine probands is determined and compared to that found in the general population. Several surveys indicated that first-and sometimes also seconddegree relatives of migraine probands show increased risk for migraine: a two-fold increased risk for migraine without aura (MO) and 1.4 for migraine with aura (MA) in the case of first-degree relatives of MO probands, and a 4-fold risk for MA in the case of first-degree relatives of MA probands [1]. An increased disease risk does not however prove heritability, since it may result from shared environmental factors. It is therefore interesting to note that at least one genetic epidemiology survey found an increased disease risk for migraine in first-degree relatives compared to spouses of migraine probands, who presumably share environmental factors at least for some time in their lives. Notably however, the relative risk for spouses was increased compared to the general population, which implies some degree of assorted mating or shared environmental influences [1]. Studies of heritability performed according to disease risk comparisons came to high rates of genetic determination, e.g. 60%-80% for MO and MA [2].Better ways of analysing heritability of migraine are studies of monozygotic versus dizygotic twins, especially when reared-together and reared-apart (adopted) identical twins are considered. Several twin studies have been performed in migraine Pasquale Montagna Pietro Cortelli Mirella MochiAbstract Epidemiological genetic, family and twin studies show that the typical migraines carry a substantial genetic risk; they are currently conceptualized as complex genetic diseases. Several genetic association and linkage studies have been performed in the typical migraines. Candidate gene studies based on "a priori" pathogenic models of migraine (migraine as a calcium channelopathy; a mitochondrial DNA disorder; a disorder in the metabolism of serotonin or dopamine; in vascular risk factors or in the inflammation cascade; etc.) did not result in uniformely accepted findings. Linkage and genome wide scans gave evidence for several genetic susceptibility loci, still however in need of confirmation. Careful dissection of the clinical phenotypes and trigger factors shall greatly help future efforts in the quest for the genetic basis of the typical migraines.

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“…These alleles may be considered as risk factors for migraine without aura in the Italian population. In a previous study, Martelletti et al [13] genotyped 45 migraine patients for HLA-DRB1 alleles and found no significant difference with controls. The number of patients examined in this study was probably too low for the detection of a statistically significant difference.…”

Section: Discussionmentioning

confidence: 92%

Association between migraine and HLA–DRB1 gene polymorphisms

et al. 2005

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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

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Chromosome 6p-encoded HLA-DR2 determinant discriminates migraine without aura from migraine with aura

Cited by 26 publications

References 33 publications

Investigation of TNFA 308G > A and TNFB 252G > A polymorphisms in genetic susceptibility to migraine

Investigation of TNFA 308G > A and TNFB 252G > A polymorphisms in genetic susceptibility to migraine

The “typical” migraines: genetic studies and some practical considerations

Association between migraine and HLA–DRB1 gene polymorphisms

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