Laboratory of Behavioral Medicine (Palanga), Neuroscience Institute, Lithuanian University of Health Sciences, Lithuania.
Department of Neurology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
J Neurol Sci. 2019 Dec 15;407:116457. doi: 10.1016/j.jns.2019.116457. Epub 2019 Sep 11.
Ischemic stroke is a major cause of premature death and chronic disability worldwide, and individual variation in functional outcome is strongly influenced by genetic factors. Neuroendocrine signaling by the hypothalamic-hypophyseal-thyroid axis is a critical regulator of post-stroke pathogenesis, suggesting that allelic variants in thyroid hormone (TH) signaling can influence stroke outcome.
To examine associations between acute ischemic stroke (AIS) outcome and allelic variants of the TH metabolizing enzymes deiodinase type 1-3 (DIO1-3) and membrane transporting organic anion polypeptide C1 (OATP1C1).
Eligible AIS patients from Lithuania (n = 248) were genotyped for ten DIO1-3 and OATP1C1 single nucleotide polymorphisms (SNPs): 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. Functional outcome was evaluated one year after index AIS using the modified Rankin Scale. Analyses were adjusted for important confounders, including serum free triiodothyronine.
After adjustment for potential confounders, the major allelic (wild-type) DIO3 genotype rs945006-TT was associated with better 1-year AIS functional outcome (odds ratio [OR] = 0.25; 95% confidence interval [CI]: 0.08-0.74; p = .013), while the wild-type OATP1C1 genotype rs10770704-CC was associated with poorer outcome (OR = 2.00, 95%CI: 1.04-3.86; p = .038).
Allelic variants in thyroid axis genes may prove useful for prognosis and treatment guidance.
缺血性脑卒中是全球范围内导致早逝和慢性残疾的主要原因，而功能预后的个体差异受遗传因素的强烈影响。下丘脑-垂体-甲状腺轴的神经内分泌信号是卒中发病机制的关键调节剂，这表明甲状腺激素（TH）信号的等位基因变异可能影响卒中结局。
研究急性缺血性脑卒中（AIS）结局与 TH 代谢酶脱碘酶 1-3（DIO1-3）和膜转运有机阴离子多肽 C1（OATP1C1）的等位基因变异之间的关联。
从立陶宛的合格 AIS 患者（n=248）中，对 10 个 DIO1-3 和 OATP1C1 单核苷酸多态性（SNP）进行基因分型：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。使用改良 Rankin 量表在指数 AIS 后一年评估功能结局。分析调整了重要的混杂因素，包括血清游离三碘甲状腺原氨酸。
在调整潜在混杂因素后，主要等位基因（野生型）DIO3 基因型 rs945006-TT 与 1 年 AIS 功能结局较好相关（比值比[OR] = 0.25；95%置信区间[CI]：0.08-0.74；p = .013），而野生型 OATP1C1 基因型 rs10770704-CC 与结局较差相关（OR = 2.00，95%CI：1.04-3.86；p = .038）。
甲状腺轴基因的等位基因变异可能对预后和治疗指导有用。
