Deiodinases, organic anion transporter polypeptide polymorphisms and ischemic stroke outcomes

Area of Science:

• Genetics
• Neurology
• Endocrinology

Background:

• Ischemic stroke (AIS) is a leading cause of death and disability globally.
• Individual recovery from stroke varies significantly due to genetic factors.
• The hypothalamic-hypophyseal-thyroid axis plays a crucial role in post-stroke recovery, indicating that thyroid hormone (TH) signaling is a potential target.

Purpose of the Study:

• To investigate the association between allelic variants of TH metabolizing enzymes (deiodinase types 1-3, DIO1-3) and the membrane transporter OATP1C1 with outcomes in acute ischemic stroke (AIS) patients.
• To identify specific genetic markers that may predict functional recovery after AIS.

Main Methods:

• Genotyping of 248 Lithuanian AIS patients for ten single nucleotide polymorphisms (SNPs) in DIO1-3 and OATP1C1 genes.
• Evaluation of functional outcome using the modified Rankin Scale one year post-stroke.
• Statistical analysis adjusted for confounders, including serum free triiodothyronine levels.

Main Results:

• The wild-type DIO3 genotype (rs945006-TT) was associated with significantly better functional outcomes one year after AIS (OR=0.25, p=0.013).
• Conversely, the wild-type OATP1C1 genotype (rs10770704-CC) was linked to poorer functional outcomes (OR=2.00, p=0.038).

Conclusions:

• Allelic variants in thyroid axis genes, specifically DIO3 and OATP1C1, show a significant association with functional outcomes following acute ischemic stroke.
• These genetic variations may serve as valuable biomarkers for predicting stroke prognosis and guiding treatment strategies.