Methylation of Migraine-Related Genes in Different Tissues of the Rat

Labruijere, Sieneke; Stolk, Lisette; Verbiest, Michaël; Vries, René de; Garrelds, Ingrid M.; Eilers, Paul H.C.; Danser, A.H. Jan; Uitterlinden, André G.; MaassenVanDenBrink, Antoinette

doi:10.1371/journal.pone.0087616

Cited by 24 publications

(20 citation statements)

References 60 publications

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“…The non-parametric Mann–Whitney test was performed to evaluated group differences with regard to DNA methylation level. Since the CpG sites within RAMP1 gene promoter region are not independent but correlated with each other [ 17 ], and the sample size was small, we did not perform the strict Bonferroni correction or other conservative approach. The receiver operating characteristic (ROC) curve and Youden criterion were used to determine the optimal cut-off point of methylation level.…”

Section: Methodsmentioning

confidence: 99%

DNA methylation of RAMP1 gene in migraine: an exploratory analysis

et al. 2015

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BackgroundReceptor activity modifying protein 1(RAMP1) is a key receptor subunit of calcitonin gene related peptide (CGRP) playing a critical role in migraine. But variations in RAMP1 gene have not been found to link with migraine. Still it is elusive that DNA methylation at RAMP1 promoter is associated with migraine.MethodsA total of 51 blood DNA samples from 26 patients with migraine and 25 matched healthy controls were collected, extracted and treated with bisulfate. Subsequently DNA methylation levels at RAMP1 promoter region were measured using Sequenom Mass ARRAY systems.ResultsAmong 13 detected CpG sites or units at RAMP1 promoter region, there were no significant differences between the migraine and control groups, but indicating a low methylation trend overall in migraine group (total average methylation level: 8.41 % ±1.92 % vs. 9.90 % ± 3.88 %, p = 0.197). Stratification analysis showed that methylation level at (+25, +27, +31, related to the transcription start site) CpG unit was higher in migraineurs with migraine family history compared to those without (13.92 % ± 5.97 % vs. 8.77 % ± 6.61 %, p = 0.034), and methylation level at (+89, +94, +96) CpG unit was lower in migraine female than that in healthy female (2.18 % ± 1.91 % vs. 5.85 % ± 5.41 %, p = 0.02). For female with methylation level at (+89, +94, +96) CpG unit below 3.50 %, the probability of being a migraine patient was significantly higher than those with methylation level above the threshold (OR: 7.313; 95%CI: 1.439-37.164).ConclusionsThis study provides the first evidence that DNA methylation at RAMP1 promoter might play a role in migraine. A low methylation trend overall was presented in migraine subjects, and two CpG units were observed to link with positive migraine family history and female migraine, respectively. Lower methlytion level at (+89, +94, +96) CpG unit may be a risk of migraine in females.

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Section: Methodsmentioning

confidence: 99%

DNA methylation of RAMP1 gene in migraine: an exploratory analysis

et al. 2015

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“…DNA methylation patterns of genes associated with migraine pathophysiology that are likely epigenetically regulated, including genes for CALCA, RAMP1, CRCP, and CALCRL, were compared in various tissues. For previously studied genes coding for CALCA and RAMP1, methylation pattern concordance was observed among all tissues, thus demonstrating that CALCA and RAMP1 gene results could be extrapolated to neurological tissue [130]; however, this result was not observed for the other two genes. Meanwhile, the authors observed high agreement between DNA methylation in rat and human leukocytes [130], indicating that it is possible to study DNA methylation in rat tissues for tissues or samples that would be difficult to obtain from humans.…”

Section: Environmental Factors and Migrainementioning

confidence: 73%

“…For previously studied genes coding for CALCA and RAMP1, methylation pattern concordance was observed among all tissues, thus demonstrating that CALCA and RAMP1 gene results could be extrapolated to neurological tissue [130]; however, this result was not observed for the other two genes. Meanwhile, the authors observed high agreement between DNA methylation in rat and human leukocytes [130], indicating that it is possible to study DNA methylation in rat tissues for tissues or samples that would be difficult to obtain from humans. In contrast, several genes encoding proteins involved in the methylation cycle, such as the methylene tetrahydrofolate reductase gene (MTHFR), have not been associated with migraine using GWAS.…”

Section: Environmental Factors and Migrainementioning

confidence: 73%

“…It is therefore unclear whether patterns of DNA methylation in blood leukocytes correlate with patterns in neurological tissue. To address this concern, Labruijere et al [130] studied DNA methylation patterns in rat leukocytes and tissues including dura mater, trigeminal ganglia, and caudal trigeminal nucleus. DNA methylation patterns of genes associated with migraine pathophysiology that are likely epigenetically regulated, including genes for CALCA, RAMP1, CRCP, and CALCRL, were compared in various tissues.…”

Section: Environmental Factors and Migrainementioning

confidence: 99%

“…In contrast, several genes encoding proteins involved in the methylation cycle, such as the methylene tetrahydrofolate reductase gene (MTHFR), have not been associated with migraine using GWAS. Nevertheless, methylation of some genes associated with migraine might be epigenetically regulated [130].…”

Section: Environmental Factors and Migrainementioning

confidence: 99%

See 2 more Smart Citations

Current Evidence on the Role of Epigenetic Mechanisms in Migraine: The Way Forward to Precision Medicine

Gazerani¹

2018

obm genet

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Interactions between genetic and environmental factors in migraine are well known and can potentially determine an individual's susceptibility to disease and responsiveness to treatment. Consequently, several epigenetic studies have been conducted to determine if and how genes are activated or inactivated in response to a diverse range of environmental migraine triggers. The results, in turn, have helped elucidate how these factors can promote or inhibit migraine progression or therapeutic response and can guide development of precision medicines for migraine treatment. This review summarizes the current evidence and latest findings (accessible mainly through Medline-PubMed) that reveal epigenetic processes contributing to migraine pathogenesis acting via various distinct mechanisms. One of the most studied mechanisms, DNA methylation within the human methylome, may provide a potential epigenetic signature for migraine. Recent basic experimental data and clinical findings will be presented here to highlight that epigenetic studies hold great potential to explain risk factors, migraine chronification, and therapeutic responses. Current challenges and unmet needs are also addressed to promote further investigation of the role of migraine epigenetics in disease pathophysiology and to discover useful biomarkers to guide development of more effective therapeutics.

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