Type II deiodinase polymorphisms and serum thyroid hormone levels in patients with mild cognitive impairment

Abstract

ABSTRACT. We investigated type II deiodinase (DIO 2 ) polymorphisms and serum thyroid hormone levels in subjects with mild cognitive impairment (MCI) in a Uygur population. We studied the DIO 2 Thr92Ala (rs225014) and ORFa-Gly3Asp (rs12885300) polymorphisms of 129 unrelated MCI cases and 131 matched controls. All subjects were genotyped using SNaPshot SNP genotyping assays. Serum thyroid hormone levels were measured by radioimmunoassay. Levels of serum triiodothyronine and thyroxine in the MCI group were significantly lower than those in the control group. Genotype and allele frequencies in the DIO 2 gene between the MCI and control groups were not significantly different. There was no association in genotype and allele frequencies of Thr92Ala between genders in both groups. ORFa-Gly3Asp genotype and allele frequencies were significantly different in patients and controls by gender. The Asp allele was less frequent among male MCI patients compared to controls (odds ratio = 0.471, 95% confidence interval = 0.261-0.848). However, female Asp carriers were more frequent among MCI patients than among controls (odds ratio = 2.842, 95% confidence interval = 1.326-6.09). Serum levels of triiodothyronine and thyroxine 5408 M. Luo et al. ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 5407-5416 (2015) were lower in individuals of the Ala/Ala genotype than in those with the Thr/Thr or Thr/Ala genotype. Serum levels of triiodothyronine were lower in male Gly/Gly carriers than in Gly/Asp or Asp/Asp carriers. Decreased serum levels of triiodothyronine and thyroxine may influence the incidence of MCI in the Uygur population. DIO 2 gene polymorphisms may play a role in the incidence of MCI in male patients.

New insights into thyroid hormone action

“…This Ala92 change in the enzyme has been predicted to impair function of the enzyme. For example, patients with mild cognitive impairment carrying the Ala92-D2 SNP showed decreased levels of circulating T3 (Luo, Zhou, Zou, Keyim, & Dong, 2015). However, four SNPs identified in patients with primary hypothyroidism on T4-treatment showed no effect on circulating TSH and fT3 (Al-azzam, Alkhateeb, Al-Azzeh, Alzoubi, & Khabour, 2013).…”

Single Nucleotide Polymorphisms in Thyroid Hormone Transporter Genes MCT8, MCT10 and Deiodinase DIO2 Contribute to Inter-Individual Variance of Executive Functions and Personality Traits

“…There are a few previous studies on the rs225014 polymorphism of DIO2 with a relationship to cognitive functions. Luo et al [64] investigated Uygur subjects with and without mild cognitive impairment and assessed the distribution of the alleles of DIO2 polymorphism in the two groups. They found a complex pattern suggesting that DIO2 gene polymorphisms may play a role in the incidence of mild cognitive impairment (MCI) in male but ▶Fig.…”

Altered Serum Marker of Thyroid Profile and Antioxidant Enzymes in Individuals Alzheimer's Disease

“…Circulation or non-nervous system tissues contain a relatively lower ratio of T3 / T4 compared to circulation or nervous tissues 9 .In the brain T3 is produced from T4 by type II deiodinase (DIO2), which is an enzyme important in preserving the intracellular T3 levels in the CNS. During hypothyroidism the expressions of DIO2 increase in the brain to maintain T3 level 10 .…”