Endothelial Nitric Oxide Synthase Haplotypes Associated with Aura in Patients with Migraine

Abstract

There is strong evidence implicating nitric oxide (NO) in the pathophysiology of migraine and aura. Therefore, genetic polymorphisms in the endothelial NO synthase (eNOS) gene have been studied as candidate markers for migraine susceptibility. We compared for the first time the distribution of eNOS haplotypes including the three clinically relevant eNOS polymorphisms (T(-786)C in the promoter, rs2070744; Glu298Asp in exon 7, rs1799983; and a 27 bp variable number of tandem repeats in intron 4) and two additional tagging single-nucleotide polymorphisms (rs3918226 and rs743506) in 178 women with migraine (134 without aura and 44 with aura) and 117 healthy controls (control group). Genotypes were determined by TaqMan allele discrimination assay, real-time polymerase chain reaction, and polymerase chain reaction followed by fragment separation by electrophoresis. The GA (rs743506) genotype was more common in the control group than in women with migraine (odds ratio = 0.47, 95% confidence interval [CI] = 0.29-0.78, p < 0.01). No significant differences were found in allele distributions for the five eNOS polymorphisms. However, the haplotypes including the variants "C C a Glu G" and the variants "C C b Glu G" were more common in women with migraine with aura than in women with migraine without aura (odds ratio = 30.71, 95% CI = 1.61-586.4 and odds ratio = 17.26, 95% CI = 1.94-153.4, respectively; both p < 0.0015625). These findings suggest that these two eNOS haplotypes affect the susceptibility to the presence of aura in patients with migraine.

The effects of endothelial nitric oxide synthase tagSNPs on nitrite levels and risk of hypertension and obesity in children and adolescents

“…[13][14][15][16][17] However, tagSNPs provide further NOS3 genetic variation, which has been previously investigated. 42,43 In fact, haplotypes including the tagSNPs rs3918226 and rs743506 were associated with other conditions involving cardiovascular alterations. 42,43 Taken together, these findings suggest pathophysiological implications for these NOS3 tagSNPs.…”

Effect of vitamin D therapy in addition to amitriptyline on migraine attacks in pediatric patients

“…Vitamin D has been shown to be associated with chronic pain. Levels of the neuroexcitator mediator, substance P, calcitonin gene-related peptide (GCRP), and nitric oxide (NO) increase in chronic pain and migraine attacks (26,27). A decrease in these mediators involved in oxidative stress has been shown to take place with vitamin D therapy.…”

Migren Hastalarında Endotelyal Nitrik Oksit Sentaz ve Anjiyotensin Dönüştürücü Enzim Gen Polimorfizmleri

“…Nöronal (nNOS) ve indüklenebilir NOS (iNOS) olmak üzere iki farklı izotipi daha vardır. Yapılan çalışmaların pek çoğu hem iNOS hem de eNOS gen polimorfizmlerinin migren ile ilişkili olmadığını göstermiştir (13,14). Ancak bir çalışmada iNOS gen polimorfizminde (a) alelinin auralı migren grubunda aurasızlara göre daha sık olduğunu bildirilmiştir (33).…”

“…Bu enzimi kodlayan genlerin polimorfizmlerinin bazal NO düzeylerini etkilediği gösterilmiştir (11). Bir çalışmada NOS gen polimorfizminin auralı migren için bağımsız bir risk faktörü olduğunu bildirirken (12), diğer çalışmalar bu ilişkiyi desteklememiştir (13,14).…”