Taroza Saulius, Rastenytė Daiva, Burkauskas Julius, Podlipskytė Aurelija, Kažukauskienė Nijolė, Patamsytė Vaiva, Mickuvienė Narseta
Laboratory of Behavioural Medicine (Palanga), Neuroscience Institute, Lithuanian University of Health Sciences, Lithuania.
Department of Neurology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
J Stroke Cerebrovasc Dis. 2020 Sep;29(9):105040. doi: 10.1016/j.jstrokecerebrovasdis.2020.105040. Epub 2020 Jun 23.
Emotional disturbances, such as anxiety and depression are common after acute ischemic stroke (AIS). Individual variation in emotional outcome is strongly influenced by genetic factors. One of pituitary axis, is the hypothalamic-pituitary-thyroid axis, a critical regulator of post-stroke recovery, suggesting that allelic variants in thyroid hormone (TH) signaling regulation can influence stroke outcome.
To determine associations between AIS emotional outcome and allelic variants of the TH metabolizing enzymes 1-3 type deiodinase (DIO1-3) and the membrane transporting organic anion polypeptide 1C1 (OATP1C1).
Eligible AIS patients from Lithuania (n=168) were genotyped for ten DIO1-3 and OATP1C1 single nucleotide polymorphisms (SNP): DIO1 rs12095080-A/G, rs11206244-C/T, and rs2235544-A/C; DIO2 rs225014-T/C and rs225015-G/A; DIO3 rs945006-T/G; OATP1C1 rs974453-G/A, rs10444412-T/C, rs10770704-C/T, and rs1515777-A/G. Emotional outcome was evaluated using the Hospital Anxiety and Depression Scale at discharge from the neurology department after experienced index AIS.
After adjustment for potential confounders, the major allelic (wild-type) DIO1-rs12095080 genotype (AA) was associated with higher odds ratio of anxiety symptoms (OR = 5.16; 95% CI: 1.04-25.58; p = 0.045), conversely, DIO1-rs11206244 wild-type genotype (CC) and wild-type OATP1C1-rs1515777 allele containing the genotypes (AA + AG) were associated with lower odds ratio of symptoms of anxiety (OR = 0.37; 95% CI: 0.14-0.96; p = 0.041 and OR = 0.30; 95% CI: 0.12-0.76; p = 0.011, respectively). Wild-type OATP1C1-rs974453 genotype (GG) was associated with higher odds ratio of symptoms of depression (OR = 2.73; 95% CI: 1.04-7.12; p = 0.041).
Allelic variants in thyroid axis genes may predict emotional outcomes of AIS.
急性缺血性卒中（AIS）后，焦虑和抑郁等情绪障碍很常见。情绪结局的个体差异受遗传因素的强烈影响。垂体轴之一是下丘脑 - 垂体 - 甲状腺轴，它是卒中后恢复的关键调节因子，这表明甲状腺激素（TH）信号调节中的等位基因变异可能影响卒中结局。
确定AIS情绪结局与TH代谢酶1 - 3型脱碘酶（DIO1 - 3）和膜转运有机阴离子多肽1C1（OATP1C1）的等位基因变异之间的关联。
对来自立陶宛的符合条件的AIS患者（n = 168）进行基因分型，检测10个DIO1 - 3和OATP1C1单核苷酸多态性（SNP）：DIO1 rs12095080 - A/G、rs11206244 - C/T和rs2235544 - A/C；DIO2 rs225014 - T/C和rs225015 - G/A；DIO3 rs945006 - T/G；OATP1C1 rs974453 - G/A、rs10444412 - T/C、rs10770704 - C/T和rs1515777 - A/G。在经历首次AIS后从神经科出院时，使用医院焦虑和抑郁量表评估情绪结局。
在对潜在混杂因素进行调整后，主要等位基因（野生型）DIO1 - rs12095080基因型（AA）与焦虑症状的较高比值比相关（OR = 5.16；95% CI：1.04 - 25.58；p = 0.045），相反，DIO1 - rs11206244野生型基因型（CC）和含有野生型OATP1C1 - rs1515777等位基因的基因型（AA + AG）与焦虑症状的较低比值比相关（OR = 0.37；95% CI：0.14 - 0.96；p = 0.041和OR = 0.30；95% CI：0.12 - 0.76；p = 0.011）。野生型OATP1C1 - rs974453基因型（GG）与抑郁症状的较高比值比相关（OR = 2.73；95% CI：1.04 - 7.12；p = 0.041）。
甲状腺轴基因中的等位基因变异可能预测AIS的情绪结局。
