Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine.
We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.
McCarthy
L C
LC
GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK. lm93678@gsk.com
Hosford
D A
DA
Riley
J H
JH
Bird
M I
MI
White
N J
NJ
Hewett
D R
DR
Peroutka
S J
SJ
Griffiths
L R
LR
Boyd
P R
PR
Lea
R A
RA
Bhatti
S M
SM
Hosking
L K
LK
Hood
C M
CM
Jones
K W
KW
Handley
A R
AR
Rallan
R
R
Lewis
K F
KF
Yeo
A J
AJ
Williams
P M
PM
Priest
R C
RC
Khan
P
P
Donnelly
C
C
Lumsden
S M
SM
O'Sullivan
J
J
See
C G
CG
Smart
D H
DH
Shaw-Hawkins
S
S
Patel
J
J
Langrish
T C
TC
Feniuk
W
W
Knowles
R G
RG
Thomas
M
M
Libri
V
V
Montgomery
D S
DS
Manasco
P K
PK
Xu
C F
CF
Dykes
C
C
Humphrey
P P
PP
Roses
A D
AD
Purvis
I J
IJ
D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D002888:Chromosomes, Human, Pair 19; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D044465:White People / Q000235:genetics
D017931:DNA Primers; D011972:Receptor, Insulin