Lack of association between oxidative stress-related gene polymorphisms and chronic migraine in an Italian population

Abstract

Migraine patients present increased risks of vascular diseases such as high blood pressure, insulin resistance, metabolic syndrome, stroke and coronary heart disease. Oxidative stress (OS) is increasingly being studied in relation to the pathophysiology of migraine, stimulated by the described association with the most frequent migraine comorbidities. Because many of the gene-encoded players of the OS balance are characterized by functional polymorphisms, it is supposed that the individual genomic profile could affect susceptibility to OS and to related pathophysiological conditions. This study aimed to characterize a panel of 10 polymorphisms in 8 OS-related genes in a chronic migraine (CM) population and healthy controls, to recognize a genetic risk in the process of migraine chronification. The sample consisted of 45 healthy women and 96 women diagnosed with CM. No deviations from the Hardy-Weinberg equilibrium were detected, or in the overall population, or in the CM group or in the control group.

Keywords:

• chronic migraine
• gene polymorphisms
• oxidative stress

Acknowledgements

This article is dedicated to the memory of our wonderful teacher and friend, D Barra, who recently passed away.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Chronic migraine (CM) is associated with an individual and socioeconomic burden much higher compared with episodic migraine. Identification of factors increasing the risk of chronification allows early set-up of prophylactic strategies.

• Oxidative stress (OS) is a complex phenomenon arising from an unbalance in the cellular redox state, which is associated with mitochondrial dysfunctions and with the pathophysiology of several diseases. Many reports show altered levels of OS markers also in migraineurs. If recognized as a determinant of migraine chronification, OS could represent a prophylactic therapeutic target and would allow therapy monitoring through determination of biochemical OS markers.

• Polymorphisms in the genes coding for anti-oxidant and/or pro-oxidant proteins are supposed to affect susceptibility to OS and to the related pathophysiological conditions. A genetic make-up increasing the individual exposure to OS could contribute to the chronification process of migraine.

• However, this study did not detect association between 10 polymorphisms involved in OS and CM.

• The candidate-gene approach used in this study cannot definitely rules out an effect of the OS genetic profile upon migraine chronification, because analysis of gene–gene interactions and gene–environment interactions, which are likely to play a deeper effect on the actual level of individual OS, could not be performed. Larger studies, including genome-wide association studies, are advisable to better depict the role of the genomic background in CM and to clarify if OS can be considered a good prophylactic target.

• In the meantime, treatments such as onabotulinumtoxinA and neuromodulation techniques appear promising approach for improved therapy of CM. In the future, larger diffusion and correct application of pharmacogenetic tests are expected to improve drug selection, enhancing efficacy and reducing side effects of migraine treatment.