Relationships of Ischemic Stroke Occurrence and Outcome with Gene Variants Encoding Enzymes of Tryptophan Metabolism.

Fanni Annamária Boros,Péter Klivényi,Rita Maszlag-Török,Ádám Annus,Mónika Szűcs,László Vécsei

doi:10.3390/biomedicines9101441

Fanni Annamária Boros, Péter Klivényi + Show 4 more

Open Access

https://doi.org/10.3390/biomedicines9101441

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Abstract

Ischemic stroke is among the leading causes of mortality and long-term disability worldwide. Among stroke risk factors the importance of genetic background is gaining interest. There is a growing body of evidence of changes of metabolite levels and enzyme activities involved in the conversion of Trp during the course of cerebral ischemia. We compared the frequencies of ten SNPs of five genes related to Trp metabolism between groups of 122 ischemic stroke patients and 120 control individuals. Furthermore, we examined the mRNA levels of TPH1, IDO1 and KYAT1 genes in peripheral venous blood with the aim of assessing (i) whether there are changes in their expression during the course of stroke and (ii) does any of their investigated SNPs have an impact on gene expression. In seven cases out of ten studied polymorphisms we detected significant differences in frequencies in relation to ischemic stroke occurrence, etiology, and clinical parameters. We also detected changes in the expression of TPH1 and IDO1 genes during the course of the disease. We found that those IDO1 variants which show a trend towards elevated mRNA level are more frequent in stroke patients than in controls. Our results are important novel observations which suggest a causal relationship between elevated IDO1 expression and stroke etiology.

Highlights

Stroke is the fourth leading cause of death worldwide and is among the leading causes of long-term adult disability [1]
We examined if any of the investigated single nucleotide polymorphism (SNP) affected the mRNA level of the corresponding gene in peripheral venous blood and compared the mRNA levels of three of the analyzed genes (TPH1, IDO1 and kynurenine aminotransferase 1 (KYAT1)) in blood samples of stroke patients collected at three different time points during the course of the disease
We present data demonstrating associations between ischemic stroke and variants of four genes (TPH1, IDO1, KYAT1 and AADAT) encoding enzymes of Trp metabolism

Summary

Introduction

Stroke is the fourth leading cause of death worldwide and is among the leading causes of long-term adult disability [1]. The majority of stroke cases are ischemic, when the occlusion of a blood vessel leads to the damage of the corresponding brain tissue. The often very severe and detrimental consequences of stroke carry a great burden because of physical disability and due to the resulting decline in cognitive and emotional abilities and arising healthcare costs [3]. It is well accepted that ischemic stroke is a multifactorial disease which has both modifiable and non-modifiable risk factors. In the group of modifiable risk factors belong diabetes, hypertension, obesity, hyperlipidemia and smoking, among several others [1]

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