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International journal of endocrinology 2 (74) 2016

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Influence of Distribution of Type I Deiodinase Gene Polymorphism on Indices of Thyroid Homeostasis in Patients with Chronic Hepatitis and Nonviral Liver Cirrhosis

Authors: Chympoi K.A. - Department of Internal Medicine, Higher State Educational Institution of Ukraine «Bukovinian State Medical University», Chernivtsi, Ukraine; Pashkovska N.V. - Department of Clinical Immunology, Allergology and Endocrinology, Higher State Educational Institution of Ukraine «Bukovinian State Medical University», Chernivtsi, Ukraine; Pavliukovych N.D. - Department of Internal Medicine, Clinical Pharmacology and Occupational Diseases, Higher State Educational Institution of Ukraine «Bukovinian State Medical University», Chernivtsi, Ukraine; Korotash I.F., Rybak O.Ya., Misechko A.I. - Higher State Educational Institution of Ukraine «Bukovinian State Medical University», Chernivtsi, Ukraine

Categories: Endocrinology

Sections: Clinical researches

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Summary

Вивчено особливості тиреоїдного гомеостазу у хворих на хронічні дифузні захворювання печінки залежно від А/С поліморфізму гена DIO1. Встановлено залежність показників тиреоїдного гомеостазу у хворих на хронічні дифузні захворювання печінки від дистрибуції А/С поліморфізму гена DIO1, а також відсутність зв’язку титру антитіл до тканини щитоподібної залози з даним поліморфізмом.

Изучены особенности тиреоидного гомеостаза у больных хроническими диффузными заболеваниями печени в зависимости от А/С полиморфизма гена DIO1. Установлена зависимость показателей тиреоидного гомеостаза у больных хроническими диффузными заболеваниями печени от дистрибуции А/С полиморфизма гена DIO1, а также отсутствие связи титра антител к ткани щитовидной железы с данным полиморфизмом.

The features of thyroid homeostasis in patients with chronic diffuse liver diseases, depending on the A/C polymorphism in DIO1 gene, have been studied. The dependence of indicators of thyroid homeostasis in patients with chronic diffuse liver diseases on the distribution of A/C polymorphism in DIO1 gene, as well as the absence of correlation of titer of antibodies to thyroid tissue and this polymorphism have been established.


Keywords

хронічні дифузні захворювання печінки, поліморфізм, тиреоїдний гомеостаз, антитіла до тканини щитоподібної залози.

хронические диффузные заболевания печени, полиморфизм, тиреоидный гомеостаз, антитела к ткани щитовидной железы.

chronic diffuse liver diseases, polymorphism, thyroid homeostasis, antibodies to thyroid tissue.

Introduction. Deiodinase enzymes are essential control points of cellular thyroid activity. It was found that certain allelic variants of type I deiodinase (DIO1) gene may increase the likelihood of violations of thyroid gland functions. But it is not still clear how polymorphism of this gene affects the development of thyroid dysfunction in patients with chronic diffuse liver diseases (СDLD).

The aim of the research was to study the features of thyroid homeostasis in patients with СDLD depending on A/C DIO1 gene polymorphism.

Material and methods. The study involved 50 patients with chronic hepatitis and liver cirrhosis.

A/C DIO1 gene polymorphism was studied by means of extraction of genomic DNA from peripheral blood leukocytes with subsequent amplification polymorphic sites by PCR with the programmable amplificator «Amply-4L» («Biocom», Moscow) with individual temperature program for each gene primers.

DNA extraction was carried out using reagents «DNA-sorbets-B» option 100 (Russia) according to instructions. Samples were prepared for PCR using a set of «АмплиСенс–200-1» (Russia). For discrimination of alleles of the DIO1 gene endonuclease restriction Bcl I was used («СибЭнзим», Russia).

Depending on the distribution of A/C DIO1 gene polymorphism patients were divided into three groups: AA-genotype carriers (17 patients), AC-genotype carriers (24 patients) and AS-genotype carriers (9 patients).

Features of thyroid homeostasis were studied by determination of serum free thyroxine (T4), free triiodothyronine (T3) and thyroid stimulating hormone (TSH), calculating the coefficient of the peripheral conversion of free thyroid hormones (T3/T4), antibodies to thyroglobulin ( TgAb) and antibodies to thyroid peroxidase (TPOAb).

The results and discussion. The level of TSH in serum of patients with HDLD was not significantly changed depending on the DIO1 gene polymorphism.

Probably 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 DIO1 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 DIO1 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.

The study of the titre TgAb determined probable growth rate in all groups of patients in reference with control values: for patients with CC-genotype – by 19,0% (P<0,001), for AC-genotype and AA-genotype – by 22,1% and 18,4% (P<0,001) respectively, without any probable inter-group differences. For AA-genotype carriers probable growth of TPOAb level in 2,9 times (P<0,001) was observed in comparison with the control group’s rate, for AC-heterozygotes in 2,8 times (P<0,001) and CC-homozygotes in 2,5 times (P<0,001).

Conclusion. Carriage of the C-allele of DIO1 gene is associated with increasing of DIO1 function, which shows the growth of T3/T4 coefficient and T3 level, reduction of T4 level. A-allele of the DIO1 gene is associated with a decrease in T3/T4 coefficient, T3 level, an increase in T4 level in blood of patients with HDLD.

A/C polymorphism of the DIO1 gene does not affect the antibodies’ titers of the thyroid tissue of patients with chronic diffuse liver disease.

Perspectives for further research. The obtained results indicate the need for creation of a differentiated approach concerning the diagnosis and treatment of thyroid homeostasis during chronic diffuse liver diseases depending on the expression of A/C polymorphism of the DIO1 gene. 


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