AN INVESTIGATION OF THE RELATIONSHIP BETWEEN THE
eNOS GENE POLYMORPHISM AND DIAGNOSED MIGRAINE
Güler S1,*, Gürkan H2, Tozkir H2, Turan N3, Çelik Y1
*Corresponding Author: Sibel Güler, M.D., Department of Neurology, Trakya University Faculty of Medicine,
Balkan Yerleşkesi, 22030 Edirne, Turkey. Tel: +90-284-236-49-81. Fax: +90-284-223-42-03. E-mail: drsibleguler@
yahoo.com
page: 49
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RESULTS
Migraine with aura was detected in 58 patients and
migraine without aura was detected in 117 patients; the
difference was statistically significantly (p <0.001).
There was no significant difference in terms of average
age of both patient and control groups, or in terms
of body mass index (BMI) (p >0.05). Moreover, there
was no statistically significant association between time
after migraine diagnosis, frequency, family history of
diagnosis of migraine, stroke and coronary artery disease,
and allele-genotype frequency of eNOS rs743506,
rs207468799, rs2070744, rs1799983, rs148554851,
rs180079 and rs3918226 gene polymorphisms (p
>0.05). Migraine attack duration was longer than 24
hours in 77.2% of migraine patients with aura, and
in 45.3% of patients with migraine without aura (p =
0.001). There was a statistically significant association
between the eNOS rs1799983 TT genotype frequency
and headache duration of longer than 24 hours (70.0%)
and headache duration of shorter than 24 hours (30.0%)
(p = 0.047). The GG genotype frequency of the eNOS
rs743506 gene polymorphism was detected to be 70.0,
30.0 and 0.0% in migraine patients with severe, mild
and light headaches, respectively (p = 0.381). The GG
genotype frequency of the eNOS rs743506 was determined
to be 70.0% in patients with headache duration
of longer than 24 hours, and as 30.0% in patients with
headache duration of shorter than 24 hours. Although
there was no statistically significant difference, the GG genotype frequency was distinctly higher in patients
with shorter duration and lighter headache attacks (p
= 0.359). The TT genotype frequency of the eNOS rs
2070744 gene polymorphism was determined to be
69.0, 20.0 and 2.0% in migraine patients with severe,
mild and light headaches, respectively, but there was
no statistically significant difference (p = 0.171). The
AA genotype frequency of the eNOS rs180079 gene
polymorphism was also detected as 68.6, 28.6 and
2.9% in migraine patients with severe, mild and light
headaches, respectively, but there was no statistically
significant association (p = 0.205). Other clinical features
of individuals in the patient and control groups
are summarized in Table 1.
There were no statistically significant differences
in association of genotype and allele frequencies
of eNOS rs743506, rs207468799, rs2070744,
rs1799983, rs148554851, rs180079, rs3918226,
rs207468799 and rs148554851 gene polymorphisms
between the patient and control group (p >0.05), as
shown in Table 2. No statistically significant differences
in genotype frequencies of the above gene
polymorphisms were detected between the migraine
with and without aura patient group and the control
group (p >0.05), as shown in Table 3.
Genotypes of patients were evaluated and haplotype
analysis was performed. Unlike other studies,
a total of seven polymorphisms were studied. This
increases the frequency of heterozygous genotypes.
Haplotype analysis was performed in individuals
with a homozygous genotype of seven polymorphism
(wild type/mutant type). Haplotype analysis could not be performed in individuals with a heterozygous
genotype because the genotypes of the parents of
patient and control groups were not known. According
to our study results, six haplotypes in the patient
group and four haplotypes in the control group were
created (Table 4).
The AGGTGGA haplotype was detected in 41
(56.9%) migraine patients, while only in 31 (43.1%)
people in the control group. No significant difference
was found between patient and control groups in
terms of frequency of carriers of this haplotype (p
>0.05). The AGGCGGG hap-lotype was detected in
two people each in the patient and control groups.
The GGGTGGA and GGGCTGG haplotypes were
observed in one person each in the patient and control
groups. The GGACTGG and AGGTTGA haplotypes
were detected only in one person in the patient group
but not in the control group (p >0.05). The AGGTGGA
haplotype was observed in 16 (39.0%) patients
with migraine with aura and 25 (61.0%) patients with
migraine without aura; the difference was not statistically
significant (p >0.05). Two (4.9%) patients with
migraine with the AGGTGGA haplotype had mild
headaches, whereas 14 (34.1%) had moderate and
25 (61.0%) had severe headaches. In terms of the
AGGTGGA haplotype, the severity of headache was
statistically significant, and was found to be severe in
61.0% (p = 0.0001). Nine (22.0%) of the patients with
migraine with the AGGTGGA haplotype had episode
duration of <12 hours, while nine (22.0%) patients
had episode duration between 12 and 24 hours, and
23 patients had episode duration of >24 hours. There
was a statistically significant difference in headache
duration in terms of AGGTGGA haplotype.
There was no statistical difference between the
AGGTGGA haplotype patients with migraine and
with or without aura, in terms of monthly headache
frequency (p >0.05). None (0.0%) of the patients
with migraine aura and the AGGTGGA haplotype
had mild headaches, while two had moderate and
14 (87.5%) had severe headaches. Two (8.0%) of the
patients without migraine had mild headaches, while
12 (48%) had moderate and 11 (44.0%) had severe
headaches. Between the AGGTGGA haplotype of
migraine with or without aura, there was a significant
difference in terms of severity of headache,
87.5% of patients with migraine with aura had severe
headaches (p = 0.050). Three (18.8%) of the patients
with migraine with aura with AGGTGGA haplotype
had episode duration of <12 hours, none of them
had episode duration between 12 and 24 hours, and
13 (81.3%) had episode duration of >24 hours. Six
(24.0%) of the patients with migraine without aura
had episode duration of <12 hours, nine (22.0%) had
episode duration between 12 and 24 hours, and 23
(56.1%) had episode duration of >24 hours. Although
there was no statistically significant difference in AGGTGGA
haplotype between patients with migraine
with and without aura, the duration of headaches
was >24 hours in 81.0% of the patients with clinical
aura (p = 0.072).
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