Joint Metabonomic and Instrumental Analysis for the Classification of Migraine Patients with 677-MTHFR Mutations

Pierangela Giustetto1, William Liboni1, Ornella Mana1, Gianni Allais2, Chiara Benedetto2, Filippo Molinari*, 3
1 Department of Neuroscience, Gradenigo Hospital, Torino, Italy
2 Women’s Headache Center, Department of Gynecology and Obstetrics, University of Torino, Torino, Italy
3 Biolab, Department of Electronics, Politecnico di Torino, Torino, Italy

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© Giustetto et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Biolab – Department of Electronics, Politecnico di Torino, Corso Duca degli Abruzzi, 24, 10129 Torino, Italy; Tel: +39 11 564 4135; Fax: +39 11 564 4217; E-mail:


Migraine is a neurological disorder that correlates with an increased risk of cerebrovascular lesions. Genetic mutations of the MTHFR gene are correlated to migraine and to the increased risk of artery pathologies. Also, migraine patients show altered hematochemical parameters, linked to an impaired platelet aggregation mechanism. Hence, the vascular assessment of migraineurs is of primary importance.

Transcranial Doppler sonography (TCD) is used to measure cerebral blood flow velocity (CBFV) and vasomotor reactivity (by an index measured during breath-holding – BHI). Aim of this study was the metabolic profiling of migraine subjects with T/T677-MTHFR and C/T677-MTHFR mutations and its correlation with CBFV and BHI.

Metabonomic multidimensional techniques were used to describe and cluster subjects. Fifty women suffering from migraine (age: 18-64; 21 with aura) underwent TCD examination, hematochemical blood analysis, Born test, and genetic tests for MTHFR mutation. Fourteen (7 with aura) had T/T677, 18 (8 with aura) had C/T677, and 18 (6 with aura) had no mutation. The total number of variables was 24.

Unsupervised and supervised techniques_showed the correlation between CBFV and BHI with mutation. Discriminant analysis allowed for classifying the subjects with 95.9% sensitivity and 89.0% specificity. Aura was not correlated to mutation or variations of instrumental data.

Our study showed that metabonomics could be effectively applied in clinical problems to show the overall correlation structure of complex systems in pathology. Specifically, our results confirmed the importance of TCD in the metabolic profiling and follow-up of migraine patients.

Keywords: Metabonomics, migraine, genetic mutations, PCA, PLS, classification, MTHFR, data mining, transcranial Doppler sonography.