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

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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