Parameters of thyroid homeostasis in patients with chronic diffuse liver diseases depending on type 1 deiodinase gene polymorphism

Abstract

Introduction: Deiodinase enzymes are important in the control, of cellular thyroid activity. It was found that certain allelic variants of type I deiodinase (D IO l) gene may increase the impairment of thyroid gland function. Still it is not clear how polymorphism of this gene affects the development of thyroid dysfunction in patients with chronic diffuse liver diseases (HDLD). Purpose: to study the features of thyroid homeostasis in patients with HDLD depending on A/C DIOl gene polymorphism. Materials and methods: The study involved 50 patients with chronic hepatitis and liver cirrhosis. A/C DIOl gene polymorphism and Prol97Leu - GPX1 gene were studied by means of extraction of genomic DNA from peripheral blood leukocytes with subsequent amplification of polymorphic sites by PCR with the programmable amplificator «Amply-4L» («Biocom», Moscow) with individual temperature program for each gene primer. DNA extraction was carried out using reagent “DNA - sorbets - B” option 100 (Russia) according to instructions. Samples were prepared for PCR using a set of «AMnnuCeHC - 200 - 1» (Russia). For discrimination of alleles of the DIOl gene endonuclease restriction Bel I was used (“Ch6 3 h3mm”, Russia). Depending on the distribution of A / C DIOl gene polymorphism patients were divided into three groups: AA-genotype carriers (17 patients), AC-genotype carriers (24 patients) and AS-genotype carriers (8 patients). Features of thyroid homeostasis were studied by determining serum free thyroxine (T4), free triiodothyronine (T3) and thyroid - stimulating hormone (TSH) and calculating the coefficient of the peripheral conversion of free thyroid hormones (T3/T4). Results and discussion: The level of TSH in serum of patients with HDLD was not significantly changed depending on the DIOl gene polymorphism. A higher level of T3 was found in carriers of the CC-genotype: in 46.6% (P <0.001) comparing with AA-genotype and 31.6% (P <0.01) comparing with AC-genotype. Content of serum T4 in patients with homozygous A-allele carrier DIOl gene significantly exceeded the corresponding parameters in patients with CC-genotype (31.3%, P <0.05). T3/T4 coefficient was also significantly changed depending on the DIOl gene polymorphism. In the group of patients with CC-genotype it was 1.5 times higher (P <0.05) than in patients with AA-genotype and 1.3 (P <0.05) times than in patients with AC-genotype. Conclusion: Carriage of the C-allele of DIOl gene is associated with increase of DIOl function, which shows growth of T3/T4 coefficient and T3 level, reduction of T4 level. A-allele of the DIOl gene is associated with a decrease in T3/T4 coefficient, T3 level, an increase in T4 level in blood of patients with HDLD.