Migraine
Conditions
Keywords
menstruation, migraine, menstrual migraine, genetics
Brief summary
The investigators hypothesize that genes that play a role in menstrual migraine can be identified using a well characterised migraine population and a comprehensive genome-wide association scan approach. The aim of the study is to identify genes, genetic regions, and the effect of hormones on expression profiles in women with menstrual migraine compared to a control population with no personal or first-degree family history of migraine. In this case control study, saliva samples will be taken from 300 cases and 300 controls for DNA analysis. Blood samples from 30 cases and 30 controls will be taken during the follicular phase as well as the luteal phase of the menstrual cycle for ribonucleic acid (RNA) analysis.
Interventions
None listed
Sponsors
Griffith University
The City of London Migraine Clinic
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
All cases and controls must: * Be over 18 years * Caucasian * Provide written, informed consent * Clearly understand and be able to comply with all the trial procedures, as required * Not have taken part in trials of any investigational products within the previous 4 weeks DNA Study: * Cases must have at least a 12-month current or past history of menstrual migraine RNA Study: * Cases must have at least a 12-month current history of menstrual migraine * Cases must have kept at least three months of headache diary data in advance of visit in order to confirm diagnosis * Controls must still be having menstrual periods
Exclusion criteria
DNA Study: * Cases and controls must not have smoked, chewed gum or consumed any food or drink in the 30 minutes prior to sample collection RNA Study: * Cases and controls will not be eligible for participation if they have: * Polycystic ovarian syndrome; * Taken any hormones or drugs in the previous three months that may affect normal hormone activity (e.g., hormonal contraceptives, hormone replacement therapy, dietary supplements such as isoflavones); * Donated or lost a significant amount of blood (\> 550 mL) within the previous 12 weeks * Additionally, controls must not have a personal or family history in any first-degree relative of current or past migraine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progesterone Receptor Gene Polymorphism PROGINS in Women With Menstrual Migraine and Women Without Migraine | 6 years | PR PROGINS |
| Estrogen Receptor 1 G594a Polymorphism in Women With Menstrual Migraine and Women Without Migraine | 6 years | ESR1 G594A |
| Estrogen Receptor 1 C325G Polymorphism in Women With Menstrual Migraine and Women Without Migraine | 6 years | ESR1 C325G |
| Menstrual Cycle Expression of PGR and ESR in Women With Menstrual Migraine and Women Without Migraine | 6 years | PgR and ESR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SYNE1 Genotype in Women With Menstrual Migraine and Women Without Migraine | 6 years | SYNE1 |
| Menstrual Cycle Expression of TNF and SYNE1 in Women With Menstrual Migraine and Women Without Migraine | 6 years | TNF and SYNE1 |
| Tumour Necrosis Factor Genotype in Women With Menstrual Migraine and Women Without Migraine | 6 years | TNF |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1 Menstrual Migraine Caucasian women with a current or past history of menstrual migraine (MM = pure menstrual migraine or menstrually-related migraine) attending the City of London Migraine Clinic | 285 |
| 2 No Migraine Caucasian women with no personal history of migraine | 300 |
| Total | 585 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Saliva Samples (DNA) | Australian samples of different genotype | 0 | 145 |
| Saliva Samples (DNA) | saliva samples not suitable for assay | 3 | 0 |
Baseline characteristics
| Characteristic | 1 Menstrual Migraine | 2 No Migraine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 285 Participants | 300 Participants | 585 Participants |
| Region of Enrollment Australia | 0 participants | 145 participants | 145 participants |
| Region of Enrollment United Kingdom | 285 participants | 155 participants | 440 participants |
| Sex: Female, Male Female | 285 Participants | 300 Participants | 585 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Estrogen Receptor 1 C325G Polymorphism in Women With Menstrual Migraine and Women Without Migraine
ESR1 C325G
Time frame: 6 years
Population: Not all samples were suitable for analysis for each outcome measure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 Menstrual Migraine | Estrogen Receptor 1 C325G Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype CC | 155 participants |
| 1 Menstrual Migraine | Estrogen Receptor 1 C325G Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype CG | 109 participants |
| 1 Menstrual Migraine | Estrogen Receptor 1 C325G Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype GG | 16 participants |
| 2 No Migraine | Estrogen Receptor 1 C325G Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype CC | 96 participants |
| 2 No Migraine | Estrogen Receptor 1 C325G Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype CG | 51 participants |
| 2 No Migraine | Estrogen Receptor 1 C325G Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype GG | 7 participants |
Comparison: Statistical analysis is of the distribution of Estrogen receptor 1 C325G polymorphism frequencies between groupsp-value: 0.18Chi-squared
Primary
Estrogen Receptor 1 G594a Polymorphism in Women With Menstrual Migraine and Women Without Migraine
ESR1 G594A
Time frame: 6 years
Population: Not all samples were suitable for analysis for each outcome measure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 Menstrual Migraine | Estrogen Receptor 1 G594a Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype GG | 196 participants |
| 1 Menstrual Migraine | Estrogen Receptor 1 G594a Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype GA | 76 participants |
| 1 Menstrual Migraine | Estrogen Receptor 1 G594a Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype AA | 8 participants |
| 2 No Migraine | Estrogen Receptor 1 G594a Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype GG | 101 participants |
| 2 No Migraine | Estrogen Receptor 1 G594a Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype GA | 43 participants |
| 2 No Migraine | Estrogen Receptor 1 G594a Polymorphism in Women With Menstrual Migraine and Women Without Migraine | Genotype AA | 6 participants |
Comparison: Statistical analysis is of the distribution of Estrogen receptor 1 G594a polymorphism frequencies between groupsp-value: 0.75Chi-squared
Primary
Menstrual Cycle Expression of PGR and ESR in Women With Menstrual Migraine and Women Without Migraine
PgR and ESR
Time frame: 6 years
Population: Matched pairs of follicular and luteal samples Not all samples were suitable for analysis for each outcome measure
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 1 Menstrual Migraine | Menstrual Cycle Expression of PGR and ESR in Women With Menstrual Migraine and Women Without Migraine | ESR expression in follicular phase | 15.98 number of genes expressed |
| 1 Menstrual Migraine | Menstrual Cycle Expression of PGR and ESR in Women With Menstrual Migraine and Women Without Migraine | ESR expression in luteal phase | 16.58 number of genes expressed |
| 1 Menstrual Migraine | Menstrual Cycle Expression of PGR and ESR in Women With Menstrual Migraine and Women Without Migraine | PGR expression in follicular phase | 9.62 number of genes expressed |
| 1 Menstrual Migraine | Menstrual Cycle Expression of PGR and ESR in Women With Menstrual Migraine and Women Without Migraine | PGR expression in luteal phase | 8.95 number of genes expressed |
| 2 No Migraine | Menstrual Cycle Expression of PGR and ESR in Women With Menstrual Migraine and Women Without Migraine | PGR expression in luteal phase | 8.69 number of genes expressed |
| 2 No Migraine | Menstrual Cycle Expression of PGR and ESR in Women With Menstrual Migraine and Women Without Migraine | ESR expression in follicular phase | 16.73 number of genes expressed |
| 2 No Migraine | Menstrual Cycle Expression of PGR and ESR in Women With Menstrual Migraine and Women Without Migraine | PGR expression in follicular phase | 9.80 number of genes expressed |
| 2 No Migraine | Menstrual Cycle Expression of PGR and ESR in Women With Menstrual Migraine and Women Without Migraine | ESR expression in luteal phase | 15.62 number of genes expressed |
p-value: >0.05t-test, 1 sided
Primary
Progesterone Receptor Gene Polymorphism PROGINS in Women With Menstrual Migraine and Women Without Migraine
PR PROGINS
Time frame: 6 years
Population: Not all samples were suitable for analysis for each outcome measure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 Menstrual Migraine | Progesterone Receptor Gene Polymorphism PROGINS in Women With Menstrual Migraine and Women Without Migraine | No PROGINS insert | 208 participants |
| 1 Menstrual Migraine | Progesterone Receptor Gene Polymorphism PROGINS in Women With Menstrual Migraine and Women Without Migraine | Heterozygote | 64 participants |
| 1 Menstrual Migraine | Progesterone Receptor Gene Polymorphism PROGINS in Women With Menstrual Migraine and Women Without Migraine | Homozygote | 8 participants |
| 2 No Migraine | Progesterone Receptor Gene Polymorphism PROGINS in Women With Menstrual Migraine and Women Without Migraine | No PROGINS insert | 112 participants |
| 2 No Migraine | Progesterone Receptor Gene Polymorphism PROGINS in Women With Menstrual Migraine and Women Without Migraine | Heterozygote | 39 participants |
| 2 No Migraine | Progesterone Receptor Gene Polymorphism PROGINS in Women With Menstrual Migraine and Women Without Migraine | Homozygote | 2 participants |
Comparison: Statistical analysis is of the distribution of PR PROGINS polymorphism frequencies between groupsp-value: 0.513Chi-squared
Secondary
Menstrual Cycle Expression of TNF and SYNE1 in Women With Menstrual Migraine and Women Without Migraine
TNF and SYNE1
Time frame: 6 years
Population: Matched luteal and follicular phase samples Not all samples were suitable for analysis for each outcome measure
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 1 Menstrual Migraine | Menstrual Cycle Expression of TNF and SYNE1 in Women With Menstrual Migraine and Women Without Migraine | TNF expression in follicular phase | 17.16 number of genes expressed |
| 1 Menstrual Migraine | Menstrual Cycle Expression of TNF and SYNE1 in Women With Menstrual Migraine and Women Without Migraine | TNF expression in luteal phase | 16.24 number of genes expressed |
| 1 Menstrual Migraine | Menstrual Cycle Expression of TNF and SYNE1 in Women With Menstrual Migraine and Women Without Migraine | SYNE1 expression in follicular phase | 21.56 number of genes expressed |
| 1 Menstrual Migraine | Menstrual Cycle Expression of TNF and SYNE1 in Women With Menstrual Migraine and Women Without Migraine | SYNE1 expression in luteal phase | 20.01 number of genes expressed |
| 2 No Migraine | Menstrual Cycle Expression of TNF and SYNE1 in Women With Menstrual Migraine and Women Without Migraine | SYNE1 expression in luteal phase | 20.06 number of genes expressed |
| 2 No Migraine | Menstrual Cycle Expression of TNF and SYNE1 in Women With Menstrual Migraine and Women Without Migraine | TNF expression in follicular phase | 17.33 number of genes expressed |
| 2 No Migraine | Menstrual Cycle Expression of TNF and SYNE1 in Women With Menstrual Migraine and Women Without Migraine | SYNE1 expression in follicular phase | 20.68 number of genes expressed |
| 2 No Migraine | Menstrual Cycle Expression of TNF and SYNE1 in Women With Menstrual Migraine and Women Without Migraine | TNF expression in luteal phase | 16.96 number of genes expressed |
p-value: >0.05t-test, 1 sided
Secondary
SYNE1 Genotype in Women With Menstrual Migraine and Women Without Migraine
SYNE1
Time frame: 6 years
Population: Not all samples were suitable for analysis for each outcome measure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 Menstrual Migraine | SYNE1 Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype TT | 24 participants |
| 1 Menstrual Migraine | SYNE1 Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype TG | 102 participants |
| 1 Menstrual Migraine | SYNE1 Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype GG | 89 participants |
| 2 No Migraine | SYNE1 Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype TT | 25 participants |
| 2 No Migraine | SYNE1 Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype TG | 54 participants |
| 2 No Migraine | SYNE1 Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype GG | 40 participants |
Comparison: Analysis of distribution of SYNE1 genotype frequencies between groupsp-value: 0.0246295% CI: [0.49, 0.95]Chi-squared
Secondary
Tumour Necrosis Factor Genotype in Women With Menstrual Migraine and Women Without Migraine
TNF
Time frame: 6 years
Population: Not all samples were suitable for analysis for each outcome measure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 Menstrual Migraine | Tumour Necrosis Factor Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype GG | 1 participants |
| 1 Menstrual Migraine | Tumour Necrosis Factor Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype GA | 40 participants |
| 1 Menstrual Migraine | Tumour Necrosis Factor Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype AA | 149 participants |
| 2 No Migraine | Tumour Necrosis Factor Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype GG | 2 participants |
| 2 No Migraine | Tumour Necrosis Factor Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype GA | 20 participants |
| 2 No Migraine | Tumour Necrosis Factor Genotype in Women With Menstrual Migraine and Women Without Migraine | Genotype AA | 32 participants |
Comparison: Analysis of distribution of TNF genotype frequencies between groupsp-value: 0.00274395% CI: [0.24, 0.75]Chi-squared