Evidence for an association between migraine and the hypocretin receptor 1 gene.
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ABSTRACT:
SUBMITTER: Rainero I
PROVIDER: S-EPMC3072499 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMany genetic and environmental factors are involved in the etiology of nicotine dependence. Although several candidate gene variations have been reported by candidate gene studies or genome-wide association studies (GWASs) to be associated with smoking behavior and the vulnerability to nicotine dependence, such studies have been mostly conducted with subjects with European ancestry. However, genetic factors have rarely been investigated for the Japanese population as GWASs. To elucidate genetic factors involved in nicotine dependence in Japanese, the present study comprehensively explored genetic contributors to nicotine dependence by using whole-genome genotyping arrays with more than 200,000 markers in Japanese subjects.ResultsThe subjects for the GWAS and replication study were 148 and 374 patients, respectively. A two-stage GWAS was conducted using the Fagerström Test for Nicotine Dependence (FTND), Tobacco Dependence Screener (TDS), and number of cigarettes smoked per day (CPD) as indices of nicotine dependence. For the additional association analyses, patients who underwent major abdominal surgery, patients with methamphetamine dependence/psychosis, and healthy subjects with schizotypal personality trait data were recruited. Autopsy specimens with various diseases were also evaluated. After the study of associations between more than 200,000 marker single-nucleotide polymorphisms (SNPs) and the FTND, TDS, and CPD, the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with FTND, with a p value of 0.0005921 in the two-stage GWAS. This possible association was replicated for the remaining 374 samples. This SNP was also associated with postoperative pain, the initiation of methamphetamine use, schizotypal personality traits, and susceptibility to goiter.ConclusionsAlthough the p value did not reach a conventional genome-wide level of significance in our two-stage GWAS, we obtained significant results in the subsequent analyses that suggest that the rs2653349 SNP (Val308Ile) could be a genetic factor that is related to nicotine dependence and possibly pain, schizotypal personality traits, and goiter in the Japanese population.
| S-EPMC4546081 | biostudies-literature
Project description:Migraine is a common neurological episodic disorder with a female-to-male prevalence 3- to 4-fold higher, suggesting a possible X-linked genetic component. Our aims were to assess the role of common variants of gamma-aminobutyric acid A receptor (GABAAR) genes, located in the X-chromosome, in migraine susceptibility and the possible interaction between them. An association study with 188 unrelated cases and 286 migraine-free controls age- and ethnic matched was performed. Twenty-three tagging SNPs were selected in three genes (GABRE, GABRA3 and GABRQ). Allelic, genotypic and haplotypic frequencies were compared between cases and controls. We also focused on gene-gene interactions. The AT genotype of rs3810651 of GABRQ gene was associated with an increased risk for migraine (OR: 4.07; 95% CI: 1.71-9.73, p=0.002), while the CT genotype of rs3902802 (OR: 0.41; 95% CI: 0.21-0.78, p=0.006) and GA genotype of rs2131190 of GABRA3 gene (OR: 0.53; 95% CI: 0.32-0.88, p=0.013) seem to be protective factors. All associations were found in the female group and maintained significance after Bonferroni correction. We also found three nominal associations in the allelic analyses although there were no significant results in the haplotypic analyses. Strikingly, we found strong interactions between six SNPs encoding for different subunits of GABAAR, all significant after permutation correction. To our knowledge, we show for the first time, the putative involvement of polymorphisms in GABAAR genes in migraine susceptibility and more importantly we unraveled a role for novel gene-gene interactions opening new perspectives for the development of more effective treatments.
| S-EPMC3764027 | biostudies-literature
Project description:A relationship between migraine without aura (MO) and patent foramen ovale (PFO) has been observed, but the neural basis underlying this relationship remains elusive. Utilizing independent component analysis via functional magnetic resonance imaging, we examined functional connectivity (FC) within and across networks in 146 patients with MO (75 patients with and 71 patients without PFO) and 70 healthy controls (35 patients each with and without PFO) to elucidate the individual effects of MO and PFO, as well as their interaction, on brain functional networks. The main effect of PFO manifested exclusively in the FC among the visual, auditory, default mode, dorsal attention and salience networks. Furthermore, the interaction effect between MO and PFO was discerned in brain clusters of the left frontoparietal network and lingual gyrus network, as well as the internetwork FC between the left frontoparietal network and the default mode network (DMN), the occipital pole and medial visual networks, and the dorsal attention and salience networks. Our findings suggest that the presence of a PFO shunt in patients with MO is accompanied by various FC changes within and across networks. These changes elucidate the intricate mechanisms linked to PFO-associated migraines and provide a basis for identifying novel noninvasive biomarkers.
| S-EPMC11364569 | biostudies-literature
Project description:In 2016, a large meta-analysis brought the number of susceptibility loci for migraine to 38. While sub-type analysis for migraine without aura (MO) and migraine with aura (MA) found some loci showed specificity to MO, the study did not test the loci with respect to other subtypes of migraine. This study aimed to test the hypothesis that single nucleotide polymorphisms (SNPs) robustly associated with migraine are individually or collectively associated with menstrual migraine (MM).Genotyping of migraine susceptibility SNPs was conducted using the Agena MassARRAY platform on DNA samples from 235 women diagnosed with menstrual migraine as per International Classification for Headache Disorders II (ICHD-II) criteria and 140 controls. Alternative genotyping methods including restriction fragment length polymorphism, pyrosequencing and Sanger sequencing were used for validation. Statistical analysis was performed using PLINK and SPSS.Genotypes of 34 SNPs were obtained and investigated for their potential association with menstrual migraine. Of these SNPs, rs2506142 located near the neuropilin 1 gene (NRP1), was found to be significantly associated with menstrual migraine (p?=?0.003). Genomic risk scores were calculated for all 34 SNPs as well as a subset of 7 SNPs that were nearing individual significance. Overall, this analysis suggested these SNPs to be weakly predictive of MM, but of no prognostic or diagnostic value.Our results suggest that NRP1 may be important in the etiology of MM. It also suggests some genetic commonality between common migraine subtypes (MA and MO) and MM. The identification of associated SNPs may be the starting point to a better understanding of how genetic factors may contribute to the menstrual migraine sub-type.
| S-EPMC5906416 | biostudies-literature
Project description:ObjectivesTo evaluate if patients with a diagnosis of vestibular migraine (VM) by the International Classification of Headache Disorders (ICHD) criteria have meaningful differences in symptomatology and disease characteristics when compared to patients with concurrent vestibular symptoms and migraine that do not meet ICHD criteria.MethodsPatients who presented for the evaluation of vertigo were provided a detailed questionnaire about dizziness and migraine symptoms. Patients were assigned to either VM cohort (met ICHD criteria for VM) or migraine headache (MH) cohort (met ICHD criteria for migraine with or without aura but not VM). Disease characteristics, symptomatology, quality of life, and perceived stress score were compared between the cohorts.ResultsThe VM cohort demonstrated a shorter duration of vertigo episodes, 11 ± 22 hours versus 84 ± 146 hours in the MH cohort. In the VM cohort, 81% reported experiencing migraine headaches during episodes of vertigo, versus 61% in the MH cohort. All patients in the VM cohort reported a previous diagnosis of migraine headache, whereas 9% of the MH cohort had not been previously diagnosed by another physician. There was no difference in quality of life or perceived stress scores between the cohorts.ConclusionsA large proportion of vertigo patients with migrainous features do not meet the ICHD criteria for VM. The differences between cohorts represent selection bias rather than meaningful features unique to the cohorts. As such, VM and MH with vestibular symptoms may exist on a spectrum of the same disease process and may warrant the same treatment protocols.
| S-EPMC8040771 | biostudies-literature
Project description:To investigate the role of three common polymorphisms in the beta2-adrenoceptor gene in migraine.Migraine has been associated with increased risk of cardiovascular disease and asthma in which beta2-adrenoceptors play an important role; beta-adrenoceptor antagonists are used in migraine prevention. However, the role of variants in the beta2-adrenoceptor gene in migraine is unclear.Association study among 23,753 white women, participating in the Women's Health Study, for whom we had information on migraine at baseline and genotype status of the polymorphisms rs1042713 (Gly16Arg), rs1042714 (Gln27Glu), rs1800888 (Thr164Ile). Migraine was self-reported and we distinguished between any history of migraine, active migraine with and without aura, and prior migraine (history of migraine but not active migraine) in our analyses.At baseline 4339 women reported any history of migraine. Of these, 3041 had active migraine (1221 migraine with aura, 1820 migraine without aura) and 1298 prior migraine. No migraine was reported by 19,414 women. Genotype- and haplotype-based analyses did not show an association of any of the gene variants tested with any history of migraine. The multivariable-adjusted odds ratios (ORs) (95% confidence intervals) for any history of migraine in the additive model were 1.0 (0.96-1.05) for rs1042713, 1.0 (0.95-1.05) for rs1042714, and 0.84 (0.68-1.05) for rs1800888. In the haplotype analysis the ORs ranged from 0.83 (0.67-1.03) to 1.01 (0.94-1.07) with Gly16-Glu27-Thr164 as the reference. We also did not find associations in the genotype- and haplotype-based analyses within migraine-specific subgroups.Our results do not support a role of 3 investigated polymorphisms in the beta2-adrenoceptor gene in migraine pathophysiology.
| S-EPMC2644736 | biostudies-literature
Project description:BackgroundPrevious studies revealed inconsistent results regarding association between migraine and cognitive impairment. In addition, previous studies found inconsistent results regarding the association between migraine and risk of dementia. Thus, the study aimed to make a meta-analysis exploring comparison result in different types of cognitive function between migraine patients and non-migraine subjects. In addition, meta-analysis was made to explore the association between migraine and risk of dementia.MethodsArticles published before June 2022 were searched in the following databases: PubMed, Web of Science, SCOPUS, EMBASE, EBSCO, PROQUEST, ScienceDirect and Cochrane Database of Systematic Reviews. Results were computed using STATA 12.0 software.ResultsMeta-analysis showed lower general cognitive function and language function in migraine group, compared to no migraine group (general cognitive function: standard mean difference (SMD) = - 0.40, 95% CI = - 0.66 to - 0.15; language: SMD = - 0.14, 95% confidence interval (CI) = - 0.27 to - 0.00), whereas the study showed no significant difference in visuospatial function, attention, executive function and memory between migraine group and no migraine group (visuospatial function: SMD = - 0.23, 95% CI = - 0.53 to 0.08; attention: SMD = - 0.01, 95% CI = - 0.10 to 0.08; executive function: SMD = - 0.05, 95% CI = - 0.16 to 0.05; memory: SMD = - 0.14, 95% CI = - 0.30 to 0.03). In addition, the meta-analysis showed a significant association between migraine and risk of dementia (odds ratio (OR)/relative risk (RR) = 1.30, 95% CI = 1.11 to 1.52).ConclusionsIn conclusion, the meta-analysis demonstrated lower general cognitive function and language function in migraine. In addition, migraine is associated with an increased risk of all-cause dementia, VaD and AD. These results suggest a significant association between migraine and cognitive impairment. Because of the association between migraine and cognitive impairment, neurological physician should be vigilant and effectively intervene in migraineurs with high risk factors of cognitive impairment to prevent the development of cognitive impairment.
| S-EPMC9317452 | biostudies-literature
Project description:ImportanceTriptans, the most efficient acute treatment for migraine attacks, are 5-HT1B/1D receptor agonists, but their precise mechanism of action is not completely understood. The extent to which triptans enter the central nervous system and bind to 5-HT1B receptors in the brain is unknown.ObjectivesTo determine the occupancy of sumatriptan to central 5-HT1B receptors, and to investigate changes in brain serotonin levels during migraine attacks.Design, setting, and participantsThis study of 8 patients in Denmark used a within-participant design and was conducted from April 20, 2015, to December 5, 2016. Participants were otherwise healthy patients with untreated episodic migraine without aura, aged between 18 and 65 years, and recruited from the general community. Data analysis was performed from January 2017 to April 2018.InterventionsAll participants underwent positron emission tomographic scans after injection of [11C]AZ10419369, a specific 5-HT1B receptor radiotracer. All participants were scanned 3 times: (1) during an experimentally induced migraine attack, (2) after a subcutaneous injection of 6-mg subcutaneous sumatriptan, and (3) on a migraine attack-free day. Scans 1 and 2 were conducted on the same study day. Each scan lasted for 90 minutes.Main outcome and measureThe primary outcome was the nondisplaceable binding potential of [11C]AZ10419369 across 7 brain regions involved in pain modulation. The binding potential reflects receptor density, and changes in binding potential reflects displacement of the radiotracer. The occupancy of sumatriptan was estimated from the 2 scans before and after sumatriptan administration.ResultsEight patients with migraine were included in the study; of these participants, 7 (87%) were women. The mean (SD) age of participants on study day 1 was 29.5 (9.2) years and on study day 2 was 30.0 (8.9) years. Sumatriptan was associated with statistically significantly reduced 5-HT1B receptor binding across pain-modulating regions (mean [SD] binding potential, 1.20 [0.20] vs 1.02 [0.22]; P = .001), corresponding to a mean (SD) drug occupancy rate of 16.0% (5.3%). Furthermore, during migraine attacks, as compared with outside of attacks, 5-HT1B receptor binding was statistically significantly associated with reduced in pain-modulating regions (mean [SD] binding potential, 1.36 [0.22] vs 1.20 [0.20]; P = .02).Conclusions and relevanceTreatment with sumatriptan during migraine attacks appeared to be associated with a decrease in 5-HT1B receptor binding, a finding that is most likely associated with the binding of sumatriptan to central 5-HT1B receptors, but the contribution of ongoing cerebral serotonin release to the lower binding cannot be excluded; the migraine attack-associated decrease in binding could indicate that migraine attacks are associated with increases in endogenous serotonin.
| S-EPMC6547094 | biostudies-literature
Project description:Genomic studies of cannabis use disorders have been limited. The cannabinoid receptor 1 gene (CNR1) on chromosome 6q14-15 is an excellent candidate gene for cannabis dependence due to the important role of the G-protein coupled receptor encoded by this gene in the rewarding effects of Delta9-tetrahydrocannabinol. Previous studies have found equivocal evidence for an association between SNPs in CNR1 and a general vulnerability to substance use disorders. We investigate the association between 9 SNPs spanning CNR1 and cannabis dependence in 1,923 individuals. Two SNPs that were previously associated with cannabis dependence in other studies were also significant with this phenotype in our analyses [rs806368 (P = 0.05) and rs806380 (P = 0.009)]. Haplotype analyses revealed the association to be largely driven by the SNP rs806380. These results suggest a role for the cannabinoid receptor 1 gene in cannabis dependence.
| S-EPMC2703788 | biostudies-literature
Project description:BackgroundThe causes of migraine remain unclear. Evidence suggests that the MAPK and PI3K/Akt signaling pathways play a role in migraine pathogenesis. However, studies on genetic polymorphisms in the two pathways associated with migraine are still limited.MethodsThis study included 226 migraineurs and 452 age- and sex-matched nonmigraine control individuals. Genotyping of 31 Single Nucleotide Polymorphisms (SNPs) in 21 genes was performed. The relationship between migraine and gene polymorphisms was analyzed by using logistic regression. SNP-SNP interactions were examined by a generalized multifactor dimension reduction (GMDR) approach. The possible role of SNPs was evaluated with gene expression data from the GTEx database.ResultsThe RASGRP2-rs2230414 GT genotype was associated with decreased migraine risk compared with the wild-type GG genotype [ORadj (95% CI): 0.674(0.458-0.989)]. PIK3R1-rs3730089 was associated with migraine in the recessive model [ORadj (95% CI): 1.446(1.004-2.083)]. The CACNA1H-rs61734410 CT genotype was associated with migraine risk [ORadj (95% CI): 1.561(1.068-2.281)]. One significant two-way SNP-SNP interaction was found (PRKCA rs2228945-BDNF rs6265) (p = 0.0107). Significant eQTL and sQTL signals were observed for the SNP rs2230414.ConclusionsThis is the first study to systematically reveal significant associations between MAPK and PI3K/Akt signaling pathway-related gene polymorphisms and migraine risk.
| S-EPMC11323340 | biostudies-literature