DNA methylation of RAMP1 gene in migraine: an exploratory analysis.
BACKGROUND
Receptor 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.


METHODS
A 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.


RESULTS
Among 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).


CONCLUSIONS
This 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.
Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Haidan District, Beijing, 100853, China.
Dongjun
D
Wan
Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Haidan District, Beijing, 100853, China.
Lei
L
Hou
Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Haidan District, Beijing, 100853, China.
Xiaofei
X
Zhang
Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Haidan District, Beijing, 100853, China.
Xun
X
Han
Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Haidan District, Beijing, 100853, China.
Min
M
Chen
Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Haidan District, Beijing, 100853, China.
Wenjing
W
Tang
Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Haidan District, Beijing, 100853, China.
Ruozhuo
R
Liu
Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Haidan District, Beijing, 100853, China.
Zhao
Z
Dong
Department of Neurology, Chinese PLA General Hospital, 28 Fuxing Road, Haidan District, Beijing, 100853, China. yusy1963@126.com.
Shengyuan
S
Yu
D000293:Adolescent; D000328:Adult; D002116:Calcitonin / Q000235:genetics / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D058262:Receptor Activity-Modifying Protein 1 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
D011498:Protein Precursors; C545502:RAMP1 protein, human; D058262:Receptor Activity-Modifying Protein 1; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide
DNA methylation; Migraine; RAMP1