Expression of PIAS Genes in Migraine Patients

DOI: https://doi.org/10.1007/s12031- 021- 01834- 6

Abstract-Summary Expression of PIAS1 was substantially lower in total migraineurs compared with controls (ratio of mean expressions (RME) = 0.18, SE = 0.29, p value < 0.001) and in both male and female migraineurs compared with sex-matched controls.

Expression of PIAS2 was lower in migraineurs without aura compared with con- trols (RME = 0.64, SE = 0.31, p value = 0.04) and in male subgroup of these patients compared with male controls (RME = 0.60, SE = 0.22, p value < 0.001).

In migraineurs with aura, downregulation of PIAS2 was only observed among

male subgroups (RME = 0.37, SE = 0.49, p value = 0.01).

PIAS3 was downregulated in total male migraineurs (RME = 0.52, SE = 0.43, p value = 0.04) and in male migraineurs with aura (RME = 0.49, SE = 0.45, p value = 0.03) compared with male controls.

34, p value < 0.001), female migraineurs (RME = 5.26, SE = 0.36, p value < 0.001), migraineurs with aura (RME = 4.24, SE = 0.42, p value < 0.001), female migraineurs

2.1 Genetics

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with aura (RME = 6.13, SE = 0.47, p value < 0.001), migraineurs without aura (RME = 3.33, SE = 0.38, p value < 0.001), and female migraineurs without aura (RME = 4.47, SE = 0.41, p value < 0.001) compared with the corresponding controls.

Extended: Expression of PIAS2 was lower in migraineurs without aura com- pared with controls and in male subgroup of these patients compared with male controls.

The present study suggests contribution of PIAS genes in the pathogenesis of migraine and warrants future studies to clarify the functional routes of their contribution.

Introduction To the role of cytokines in the mediation of immune functions, the extensive expres- sion of cytokine receptors in almost all cells of the central nervous system indicates their impact in this system.

Protein inhibitor of activated STAT (PIAS) constitutes a family of proteins with

fundamental roles in the regulation of cytokine signaling.

To STAT signaling, a number of transcription factors in NF-κB pathway are sub- ject of regulation by PIAS proteins (Kato Jr and others [55]; Bao and others [56]).

The impact of PIAS genes in the pathophysiology of migraine has not been

understood.

Based on the importance of PIAS genes in the regulation of immune reactions, we designed the current gene expression experiment to quantify expression amounts of PIAS transcripts in the circulation of patients with migraine versus normal matched controls.

Materials and Methods The current study was performed on samples gathered from 96 patients with migraine (15 men and 81 women, age [mean ± SD] = 37.47 ± 11.94, 46 patients without aura and 50 with aura).

All patients were in attack-free periods at the time of blood sampling. Controls were matched with cases in their age. All case and control subjects signed informed consent forms. Peripheral blood samples were acquired from patients with migraine and

controls.

RNA was extracted from all samples using the GeneAll kit (Seoul, Korea). Expression amounts of PIAS genes were measured in migraineurs and control subjects using the Ampliqon prepared master mix (Odense, Denmark) and TaqMan probes.

Transcript levels of PIAS1–PIAS4 genes were calculated in relation to the refer-

ence gene using Ct and efficiency values.

Results Expression of PIAS1 was substantially lower in total migraineurs compared with controls (ratio of mean expressions (RME) = 0.18, SE = 0.29, p value < 0.001) and in both male and female migraineurs compared with sex-matched controls.

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2 Mechanisms

Expression of PIAS2 was lower in migraineurs without aura compared with con- trols (RME = 0.64, SE = 0.31, p value = 0.04) and in male subgroup of these patients compared with male controls (RME = 0.60, SE = 0.22, p value < 0.001).

In migraineurs with aura, downregulation of PIAS2 was only observed among

male subgroups (RME = 0.37, SE = 0.49, p value = 0.01).

PIAS3 was downregulated in total male migraineurs (RME = 0.52, SE = 0.43, p value = 0.04) and in male migraineurs with aura (RME = 0.49, SE = 0.45, p value = 0.03) compared with male controls.

Discussion We reported downregulation of PIAS1 in total migraineurs compared with controls and in both male and female migraineurs compared with sex-matched controls.

The observed downregulation of PIAS1 in migraineurs might participate in the

pathogenesis of this disorder through alteration in the activity of STAT1.

Expression of PIAS2 was lower in migraineurs without aura compared with con-

trols and in male subgroup of these patients compared with male controls.

In migraineurs with aura, downregulation of PIAS2 was only observed among

male subgroups.

Consistent with similar levels of PIAS genes between patients with and without aura, expression of these genes could not distinguish between these two subclasses of migraine.

The present study suggests contribution of PIAS genes in the pathogenesis of migraine and warrants future studies to clarify the functional routes of their contribution.

Acknowledgement A machine generated summary based on the work of Ghafouri-Fard, Soudeh; Hesami, Omid; Nazer, Naghme; Sayad, Arezou; Taheri, Mohammad. 2021  in Journal of Molecular Neuroscience.

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