Effect of DIO2 Gene Polymorphism on Thyroid Hormone Levels and Its Correlation with the Severity of Schizophrenia in a Pakistani Population

Int J Mol Sci. 2024 Feb 5;25(3):1915. doi: 10.3390/ijms25031915.

Abstract

Low levels of triiodothyronine (T3) in the brain lead to increased dopamine receptor sensitivity, potentially resulting in schizophrenia. Iodothyronine deiodinase 2 (DIO2) is the only enzyme which converts tetraiodothyronine (T4) to T3 in the brain. DIO2 polymorphism of rs225014 results in the expression of non-functioning DIO2. Therefore, this study aimed to investigate the association of rs255014 with schizophrenia and its impact on thyroid hormone levels. This study included 150 schizophrenia cases and 150 controls. DNA was extracted from blood and subjected to PCR and amplicon sequencing. Serum thyroid profiles were determined using chemiluminescent magnetic microparticle immunoassay. Statistical analyses involved independent sample t-tests, Chi-square, and Pearson's correlation tests. The results revealed a higher frequency of the reference genotype (TT) in controls compared to cases (p < 0.05). However, rs225014 did not influence serum thyroid levels or the severity of schizophrenia (p > 0.05). Interestingly, control subjects exhibited significantly higher T3 levels (p < 0.001) than cases. Regardless of the genotype (TT or CC), the control group had higher mean T3 levels than the corresponding case group (p < 0.05). In conclusion, rs225014 is associated with schizophrenia and has no effect on serum thyroid hormone levels.

Keywords: PANSS; genotyping; iodothyronine deiodinase 2; rs225014; tetraiodothyronine (T4); triiodothyronine (T3).

MeSH terms

  • Humans
  • Iodide Peroxidase / genetics
  • Iodothyronine Deiodinase Type II* / genetics
  • Pakistan
  • Polymorphism, Single Nucleotide
  • Schizophrenia* / genetics
  • Thyroid Gland* / metabolism
  • Thyroid Hormones
  • Thyroxine
  • Triiodothyronine

Substances

  • Iodide Peroxidase
  • Iodothyronine Deiodinase Type II
  • Thyroid Hormones
  • Thyroxine
  • Triiodothyronine
  • DIO2 protein, human

Supplementary concepts

  • Pakistani people