Polymorphisms of iodothyronine deiodinases (DIO1, DIO3) genes are not associated with recurrent depressive disorder

Abstract

Background: Depressive disorder is characterized by disturbances in the hypothalamic-pituitary-thyroid (HPT) axis and in the metabolism of thyroid hormones (TH). The evidence for changes in TH levels is observed in human sera and cerebrospinal fluid as well as in animal model studies. Iodothyronine deiodinases (DIOs) type 1, 2 and 3 (DIO1, DIO2, DIO3) are important enzymes for the synthesis and determination of TH concentration. This study aims to examine the link between recurrent depressive disorders (rDD) and two functionally known polymorphisms DIO1a-C/T (rs11206244) and DIO1b-A/G (rs12095080) within the DIO1 gene encoding DIO1 and two polymorphisms DIO3-C/T (rs17716499), DIO3-A/C (rs7150269) within the DIO3 gene encoding DIO3.

Methods: Both variants were genotyped in 254 rDD patients and 197 healthy subjects using polymerase chain reaction. Basic methods and statistical analyses were used to estimate genetic variants in the risk of the disease.

Results: No significant associations were found between the polymorphisms examined here and rDD. There were no significant associations between genotypes distribution and demographic/medical variables. Odds ratios (ORdis) and corresponding 95% confidence interval (95% CI) were calculated, for example: for CC genotype of DIO1a C/T (ORdis=0.86, 95% CI: 0.59, 1.25).

Conclusion: Functional variants within the DIO1 gene, which affect TH levels and polymorphisms in DIO3, are not confirmed to be associated with rDD. Nevertheless, considering previous data which indicate that the DIO1 gene is related to the depression, further studies on a larger sample size are recommended.

Keywords: Polymorphism; Recurrent depressive disorder; Type 1 and 3 iodothyronine deiodinases.