Introduction
Patients (M/F)
|
Headache subtype
|
Healthy controls (M/F)
|
Mean age (years)
|
Country, Race-Ethnicity
|
Polymorphism
|
Comment
|
Reference
|
---|---|---|---|---|---|---|---|
62 (11/51) | -Migraine with aura (33) | 64 (14/50) | -Patients (32 ± 5.2) | Turkey, Asian | rs4680 | Association between the Met allele and migraine (P = 0.013) and with family history of migraine (P = 0.003). | Emin Erdal et al., 2001 [13] |
-Migraine without aura (29) | |||||||
-Controls (30.7 ± 6.3) | |||||||
982 (346/636) | -Migraine (305) | 1468 | -Patients (46.8) | Norway, Caucasian | rs4680 | No association with migraine. | Hagen et al., 2006 [14] |
Association of the Val/Val genotype with non-migrainous headache in female patients (P = 0.04). | |||||||
-Non-migrainous headache (677) | |||||||
-Controls (55.5) | |||||||
219 | -Migraine with aura (92) | 144 | - | Germany Caucasian | rs4680 | No association. | Mössner et al., 2006 [15] |
-Migraine without aura (127) | |||||||
204 | -Chronic daily headache with drug abuse (103) | 117 | -Patients (range 23-81) | Italy Caucasian | rs4680 | No association. | Cevoli et al., 2006 [16] |
-Migraine without aura without drug abuse (101) | |||||||
-Controls (over 40) | |||||||
97 | Migraine without aura (97) | 94 | - | Korea Asian | rs4680 | Met allele associated with a higher pain intensity of headache (P = 0.001) and nausea/vomiting occurring (P = 0.026). | Park et al., 2007 [17] |
263 | Migraine without aura (55.9%) | 274 | -Patients (37 ± 16) | Spain Caucasian | rs2020917 | No association. | Corominas et al., 2009 [18] |
rs933271 | |||||||
rs1544325 | |||||||
259 | Migraine without aura (61.4%) | 287 | -Controls (55 ± 18) | rs740603 | |||
rs740601 | |||||||
rs4680 | |||||||
rs4646316 | |||||||
rs174696 | |||||||
rs165774 | |||||||
rs9332377 | |||||||
rs4485648 | |||||||
270 | Migraine with aura (270) | 272 | - | Germany Caucasian | rs933271 | No association. | Todt et al., 2009 [19] |
rs740603 | |||||||
rs4680 | |||||||
rs4646316 | |||||||
rs165774 | |||||||
rs5993889 | |||||||
1132 (240/892) | -Females with hormonally modulated migraine (464) | 608 (258/350) | Patients (range 18-50) | USA, White race ~ 90% | rs4680 | Significant association with migraine (P = 0.001) and hormonally modulated migraine (P = 0.03) | Sullivan et al., 2013 [20] |
Controls (range 19-50) | |||||||
-Females with nonhormonally modulated migraine (364) | |||||||
198 (40/158) | -1st cohort: Migraine without aura (75) | - | - | Italy Caucasian | rs4680 | Significant association between the Val/Val genotype and response to triptans. | Cargnin et al., 2013 [21] |
-2nd cohort: Migraine without aura (111) | |||||||
Migraine with aura (12) |
Findings
Populations
Assessment of migraineurs’ clinical characteristics
DNA extraction and genotyping
Statistics
Study results
N
|
rs4680 genotypes (
%
)
|
rs4680 alleles (%)
|
HW (P value)
| ||||
---|---|---|---|---|---|---|---|
AA (Met/Met)
|
AG (Met/Val)
|
GG (Val/Val)
|
A
|
G
| |||
Controls | 132 | 23 (17.4) | 65 (49.2) | 44 (33.3) | 111 (42.0) | 153 (58.0) | 0,90 |
All patients with migraine | 380 | 78 (20.5) | 192 (50.5) | 110 (28.9) | 348 (45.7) | 412 (54.3) | 0,73 |
Migraine with Aura | 65 | 15 (23.1) | 30 (46.1) | 20 (30.8) | 60 (46.2) | 70 (53.8) | 0,56 |
Migraine w/out Aura | 189 | 41 (21.7) | 96 (50.8) | 52 (27.5) | 178 (47.1) | 200 (52.9) | 0,79 |
Chronic Migraine | 126 | 22 (17.5) | 66 (52.4) | 38 (30.1) | 110 (43.7) | 142 (56.3) | 0,47 |
N
|
rs4818 genotypes (
%
)
|
rs4818 alleles (
%
)
|
HW (P value)
| ||||
CC (Leu/Leu)
|
CG (Leu/Leu)
|
GG (Leu/Leu)
|
C
|
G
| |||
Controls | 132 | 30 (22.7) | 76 (57.6) | 26 (19.7) | 136 (51.5) | 128 (48.5) | 0,08 |
All patients with migraine | 380 | 111 (29.3) | 197 (51.8) | 72 (18.9) | 419 (55.1) | 341 (44.9) | 0,35 |
Migraine with Aura | 65 | 21 (32.3) | 30 (46.2) | 14 (21.5 ) | 72 (55.4) | 58 (44.6) | 0,59 |
Migraine w/out Aura | 189 | 50 (26.5) | 104 (55.0) | 35 (18.5) | 204 (54.0) | 174 (46.0) | 0,14 |
Chronic Migraine | 126 | 40 (31,7) | 63 (50.0) | 23 (18.3) | 143 (56.7) | 109 (43.3) | 0,84 |
Migraine with Aura
|
Migraine w/out Aura
|
Chronic Migraine
| |||||||
---|---|---|---|---|---|---|---|---|---|
Model
|
rs4680 genotypes
|
OR (95% CI)
|
P-value
|
rs4680 genotypes
|
OR (95% CI)
|
P-value
|
rs4680 genotypes
|
OR (95% CI)
|
P-value
|
Codominant | G/G | 1.00 | 0.65 | G/G | 1.00 | 0.44 | G/G | 1.00 | 0.87 |
A/G | 1.02 (0.51-2.01) | A/G | 1.25 (0.75-2.08) | A/G | 1.16 (0.67-2.01) | ||||
A/A | 1.43 (0.62-3.32) | A/A | 1.51 (0.79-2.89) | A/A | 1.11 (0.53-2.29) | ||||
Dominant | G/G | 1.00 | 0.72 | G/G | 1.00 | 0.26 | G/G | 1.00 | 0.61 |
A/G-A/A | 1.12 (0.59-2.13) | A/G-A/A | 1.32 (0.81-2.13) | A/G-A/A | 1.14 (0.68-1.94) | ||||
Recessive | G/G-A/G | 1.00 | 0.35 | G/G-A/G | 1.00 | 0.34 | G/G-A/G | 1.00 | 0.97 |
A/A | 1.42 (0.68-2.95) | A/A | 1.31 (0.74-2.32) | A/A | 1.01 (0.53-1.93) | ||||
Overdominant | G/G-A/A | 1.00 | 0.68 | G/G-A/A | 1.00 | 0.78 | G/G-A/A | 1.00 | 0.66 |
A/G | 0.88 (0.49-1.60) | A/G | 1.06 (0.68-1.66) | A/G | 1.12 (0.68-1.82) | ||||
Log-additive | --- | 1.18 (0.77-1.79) | 0.44 | --- | 1.23 (0.89-1.70) | 0.2 | --- | 1.07 (0.75-1.52) | 0.72 |
Model
|
rs4818 genotypes
|
OR (95% CI)
|
P-value
|
rs4818 genotypes
|
OR (95% CI)
|
P-value
|
rs4818 genotypes
|
OR (95% CI)
|
P-value
|
Codominant | C/C | 1.00 | 0.27 | C/C | 1.00 | 0.75 | C/C | 1.00 | 0.24 |
C/G | 0.56 (0.28-1.14) | C/G | 0.82 (0.48-1.41) | C/G | 0.61 (0.34-1.09) | ||||
G/G | 0.77 (0.33-1.81) | G/G | 0.81 (0.41-1.59) | G/G | 0.66 (0.32-1.38) | ||||
Dominant | C/C | 1.00 | 0.15 | C/C | 1.00 | 0.45 | C/C | 1.00 | 0.095 |
C/G-G/G | 0.62 (0.32-1.19) | C/G-G/G | 0.82 (0.49-1.38) | C/G-G/G | 0.63 (0.36-1.09) | ||||
Recessive | C/C-C/G | 1.00 | 0.76 | C/C-C/G | 1.00 | 0.79 | C/C-C/G | 1.00 | 0.79 |
G/G | 1.12 (0.54-2.32) | G/G | 0.93 (0.53-1.63) | G/G | 0.92 (0.49-1.71) | ||||
Overdominant | C/C-G/G | 1.00 | 0.13 | C/C-G/G | 1.00 | 0.65 | C/C-G/G | 1.00 | 0.2 |
C/G | 0.63 (0.35-1.15) | C/G | 0.90 (0.58-1.41) | C/G | 0.73 (0.44-1.19) | ||||
Log-additive | --- | 0.84 (0.54-1.31) | 0.45 | --- | 0.89 (0.64-1.25) | 0.51 | --- | 0.79 (0.55-1.14) | 0.21 |