Deiodinases, organic anion transporter polypeptide polymorphisms and ischemic stroke outcomes

Background: 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.

Aim: 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).

Methods: 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.

Results: 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).

Conclusion: Allelic variants in thyroid axis genes may prove useful for prognosis and treatment guidance.