Post-Stroke Fatigue May Be Associated with the Promoter Region of a <b><i>Monoamine Oxidase A </i></b>Gene Polymorphism

Abstract

Background: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. Methods: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A). Results: Among the 373 patients, 164 (44%) had PSF. All patients were ethnic Koreans. Of the 6 polymorphisms examined, only one marker, that is, low-activity MAO-A was associated with PSF (p < 0.05) in female patients. Multiple logistic regression analyses showed that post-stroke depression (PSD; 95% CI 1.561-14.323, p = 0.006) and low MAO-A activity (95% CI 0.166-0.722, p = 0.005) were factors associated with PSF in female patients, whereas only PSD (95% CI 5.511-65.269, p = 0.000) was associated with PSF in male patients. Conclusions: Our findings suggest that PSF may be associated with a genetic polymorphism involving MAO-A, at least in female stroke patients.

Prevalence of fatigue after stroke: A systematic review and meta-analysis

“…In one review, this is attributed to cultural differences in psychosocial factors rather than epidemiological determinants such as stroke type, though this review has found it to be a factor. 42 This is evident as our results show that most of the included studies in Asia have participants with only ischaemic stroke (n = 6), [31][32][33][50][51][52] whereas those in the Europe include patients with either both types of stroke (n = 11) or only haemorrhagic stroke (n = 4). [34][35][36]43,44,[47][48][49][53][54][55][56][57][58] A post-hoc sensitivity analysis supporting this demonstrates that studies in Europe that only included patients with ischaemic stroke have a similar PSF proportion to the ones conducted in Asia (37% vs 37%).…”

“…29,30 Most studies had a pre-specified aim to estimate fatigue prevalence except seven papers that focused on assessing the contributing factors of the condition. 21,[31][32][33][34][35][36] In terms of quality, the majority of studies had a medium to high-quality score of five or above out of nine (n = 20) (Figure 2). The most failed criterion was appropriate sampling as only two papers had a representative sample, with either a population-based or randomised sample, whereas the majority had a consecutive sampling.…”

Temporal Associations between Fatigue, Depression, and Apathy after Stroke: Results of the Cognition and Affect after Stroke, a Prospective Evaluation of Risks Study

“…The FSS has been validated in stroke patients [24], and based on previous studies, a cut-off score ≥4 was applied to indicate PSF [5, 25]. …”

Risk Factors and Imaging Mechanisms of Fatigue After Mild Ischemic Stroke: An Exploratory Study From a Single Chinese Center

“…Concerning the biological mechanisms of post-stroke fatigue, some studies proposed that the immune response after ischemic stroke may predict the occurrence of post-stroke fatigue ( 29 , 30 ). In Korean patients, it was found that post-stroke fatigue may be associated with genetic polymorphisms within the MAO-A gene in females ( 31 ). Hama et al showed that the monoamine neural network can be divided into catecholamine and serotonin branches, which are related to each other anatomically and functionally, and may affect the development of post-stroke fatigue and emotional disorders ( 14 ).…”