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Endothelial Nitric Oxide Synthase (Glu298Asp) Polymorphism is an Independent Risk Factor for Migraine with Aura


  • Barbara Borroni MD,

  • Renata Rao MD,

  • Paolo Liberini MD,

  • Elisabetta Venturelli MD,

  • Michela Cossandi MD,

  • Silvana Archetti PhD,

  • Luigi Caimi PhD,

  • Alessandro Padovani MD, PhD

  • From the Department of Medical Sciences, Neurological Clinic, University of Brescia, Brescia, Italy (Drs. Borroni, Rao, Liberini, Venturelli, Cossandi, and Padovani) and Department of Biotechnology, III Laboratory of Analysis, University of Brescia, Brescia, Italy (Drs. Archetti and Caimi).

Address all correspondence to Dr. Barbara Borroni, MD, Neurologic Clinic, University of Brescia, Spedali Civili, 1, Brescia 25100, Italy.


Objective.—The aim of the present study was to evaluate whether the functional endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism, which has been demonstrated to decrease the endothelial NOS activity, might be a risk factor for migraine.

Background.—It has widely demonstrated that nitric oxide (NO) is involved in migraine pathogenesis. Several genetic risk factors have been associated with migraine, but no study has unraveled a possible relationship between migraine and eNOS Glu298Asp.

Methods.—One hundred fifty-six migraine patients and 125 healthy nonheadache volunteers entered the study. Demographic and clinical characteristics were carefully recorded, and a neurological workup was performed.

Results.—eNOS AspAsp homozygous patients had a 3-fold time risk for migraine with aura (MA) when compared to migraine without aura (MO) patients (OR-3.02, 95% CI-1.21 to 7.51), and more than 2-fold time increased risk when compared to control subjects (OR-2.21, 95% CI-1.00 to 5.04).

In migraine patients, no difference in age at onset, mean attack's intensity, family history for any of the studied comorbidities, or the presence of comorbidities was found in eNOS AspAsp homozygous compared to eNOS GluGlu or eNOS GluAs carriers.

Conclusions.—Homozygous Asp298, a common variant of the eNOS gene, is an independent risk factor for MA in this study population.