OBJECTIVE: Thyroid diseases are among the most common endocrinopathies and metabolic disorders. Hypothyroidism is caused by insufficient production of thyroid hormones with a higher prevalence in women. Causes for the development of endocrine diseases may be mutations in genes that encode peptide hormones. The aim of this scientific study was to determine the genotype and allele frequencies of the rs104893657 variant of the PAX8 gene and to determine the genotype versus phenotype association. METHODS: The study population consisted of 135 women from northeastern Slovakia who were divided on the basis of screening into two groups: a control group without diagnosed hypothyroidism (CG = 67) and a group of women with hypothyroidism (HY = 68). Biochemical markers - thyroid-stimulating hormone (TSH), prealbumin (PREA), calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) were determined using Cobas Integra 400 plus, Cobas e411 analysers (Roche). Genotyping was performed using TaqMan® SNP Genotyping Assay instrument 7500 Fast Real-Time PCR Systems (Applied Biosystem). RESULTS: Student's t-test revealed a statistically significant difference between CG and HY in biochemical parameters: TSH (p < 0.001), P (p = 0.008). By Chi-square test we found no statistically significant difference in the representation of genotypes (p = 0.788) in the rs104893657 polymorphism of PAX8 gene. The T allele was not associated with hypothyroidism in Slovak women (p = 0.548). In CC genotype we found statistically significant difference between CG and HY in parameters TSH (p < 0.001) and P (p = 0.006). CONCLUSION: The mutant T allele was detected at low frequency in both groups of women studied. The association of the T allele with the development of hypothyroidism in Slovak women was not confirmed. The results of this work provide initial information on the distribution of genotypes and alleles in the studied variant of PAX8 gene in the Slovak female population.

AGEL Hospital Kosice Saca Kosice Slovak Republic

Department of Biology Faculty of Education J Selye University Komarno Slovak Republic

Department of Biology Faculty of Humanities and Natural Sciences University of Presov Presov Slovak Republic

Department of Public Health and Hygiene Faculty of Medicine Pavol Jozef Safarik University Kosice Slovak Republic

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Taylor P, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan C, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018 May;14(5):301-16. PubMed DOI

Hussian BI, Hadi MA, Al-Harbi HJ. The association of TSHR gene rs2268458 polymorphism with hypothyroidism in females of Babylon Province-Iraq. J Univ Babylon. 2018 Oct 10;26(8):7-18. DOI

Kiňová S, Koreň M. [Thyropathies in the general practitioner's clinic]. Via practica. 2016;13(6):252-5. Slovakia.

Vanderpump MPJ. The epidemiology of thyroid disease. Brit Med Bull. 2011;(99):39-51. PubMed DOI

Tomer Y. Genetic susceptibility to autoimmune thyroid disease: past, present, and future. Thyroid. 2010 Jul;20(7):715-25. DOI

Ye L, Ning G. The molecular classification of hereditary endocrine diseases. Endocrine. 2015 Dec;50(3):575-9. PubMed DOI

Vincenzi M, Camilot M, Ferrarini E, Teofoli F, Venturi G, Gaudino R, et al. Identification of a novel pax8 gene sequence variant in four members of the same family: from congenital hypothyroidism with thyroid hypoplasia to mild subclinical hypothyroidism. BMC Endocrin Disord. 2014 Aug;14:69. doi: 10.1186/1472-6823-14-69. PubMed DOI

Liu S, Wang X, Zou H, Ge Y, Wang F, Wang Y, et al. Identification and characterization of novel PAX8 mutations in Congenital Hypothyroidism (CH) in a Chinese population. Oncotarget. 2017 Jan 31;8(5):8707-16. PubMed DOI

Van Vliet G. Development of the thyroid gland: lessons from congenitally hypothyroid mice and men. Clin Gen. 2003 Jun;63(6):445-55. PubMed DOI

Qian F, Li GY, Wu XJ, Jia Q, Lyu GT, Wang ML, et al. Novel non-synonymous mutations of PAX8 in a cohort of Chinese with congenital hypothyroidism. Chin Med J (Engl). 2019 Jun 9;132(11):1322-7. PubMed DOI

Li M, Wang F, Wang X, Zang Y, Liu W, Wang F, et al. Genetic testing of PAX8 mutations associated with thyroid dysgenesis in Chinese congenital hypothyroidism patients. Endokrynologia Polska. 2020 Dec;71(2):153-9. PubMed DOI

Kankana DE. Waist circumference, waist-hip ratio and Body Mass Index in assessing nutritional status and central obesity of adolescent. Glob J Archeol Anthropol. 2017 March 15;1(1):5-8. DOI

Buková A, Chovanová E, Küchelová Z, Junger J, Horbacz A, Majherová M, et al. Association between educational level and physical activity in chronic disease patients of eastern Slovakia. Healthcare (Basel). 2021;9(11):1447. doi: 10.3390/healthcare9111447. PubMed DOI

Savita S, Geeta A, Kattaria SK, Joya H, Dhadich A. A study of anthropometric parameters, skin and its appendages in hypothyroid patients in Western Rajasthan Population. Pharma Innov J. 2014 Nov 30;3(10):88-93.

Azevêdo LM, De Oliveira MF, Dos Santos M, Adães Mota ADS, Rabelo M, Hemmings S, et al. Anthropometric profile of sedentary women with and without hypothyroidism. Rev Andal Med Deporte. 2016 Sept;11(2):47-92. DOI

Fox CS, Pencina MJ, D'Agostino RB, Murabito JM, Seely EW, Pearce EN, et al. Relations of thyroid function to body weight. Arch Intern Med. 2008 March;168(6):587-92. PubMed DOI

Milionis A, Milionis CH. Correlation between body mass index and thyroid function in euthyroid individuals in Greece. ISRN Biomarkers. 2013 Sept 23;(2013):651494. doi: 10.1155/2013/651494. DOI

Gupta G, Sharma P, Kumar P, Itagappa M, Sharma R. A correlation between thyroid stimulating hormone and body mass index in women with subclinical hypothyroidism. Asian J Pharm Clin Res. 2015 May 18;8(4):206-8.

Tóthová C, Nagy O. Transthyretin in the Evaluation of health and disease in human and veterinary medicine. In: Gaze DC, editor. Pathophysiology - altered physiological states. London (UK): IntechOpen; 2017. p. 51-67. DOI

Henze A, Homann T, Serteser M, Can O, Sezgin O, Coskun A, et al. Post-translational modifications of transthyretin affect the triiodonine-binding potential. J Cell Mol Med. 2015 Feb;19(2):359-70. DOI

Mane AY, Bhagwat VR. Serum enzymes and liver funtion tests in thyroid disorders. Biomedicine. 2011 Oct 11;31(4):517-22.

Prathyusha U, Priya BD. Association of acid and alkaline phosphatase among the thyroid patients. Asian J Pharm Clin Res. 2013 Sept 1;6(4):37-8.

Yadav A, Arora S, Saini V, Arora MK, Singh R, Bhattacharjee J. Influence of thyroid hormones on biochemical parameters of liver function: a case-control study in North Indian population. Internet J Med Update. 2013 Feb 1;8(1):4-8.

Rewatkar M, Tadas A, Agrawal S, Nimbarte. Implication of thyroid dysfunction on liver enzymes. Glob J Res Anal. 2020 March;9(3):39-40.

Susanna TY, Sagayaraj A, Shashidhar KN, Gomathi M. A correlative study of thyroid profile and mineral status in patients with hypothyroidism - a hospital based case control study. Asian J Pharm Clin Res. 2016 Jan;9(3):292-4.

Di Palma T, Nitsch R, Mascia A, Nitsch L, Di Lauro R, Zannini M. The paired domain-containing factor Pax8 and the homeodomain-containing factor TTF-1 directly interact and synergistically activate transcription. J Biol Chem. 2003 Jan 31;278(5):3395-402. PubMed DOI

Alcántara-Ortigoza MA, Del Angel AG, Martínez-Cruz V, Vela-Amieva M, Sánchez-Pérez C, Moreno-Rojas R, et al. Molecular analysis of the PAX8 gene in a sample of Mexican patients with primary congenital hypothyroidism: identification of the recurrent p.Arg31His mutation. Clin Endocrinol. 2012 Jan;76(1):148-50. PubMed DOI

Komatsu M, Takahashi T, Takahashi M, Nakamura M, Takahashi I, Takada G. Thyroid dysgenesis caused by PAX8 mutation: the hypermutability with CpG dinucleotides at codon 31. J Pediatr. 2001 Oct;139(4):597-9. PubMed DOI

Ramos HE, Carré A, Chevrier L, Syinnai G, Tron E, Cerqueira TLO, et al. Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations. Eur Soc Endocrinol. 2014 Oct;171(4):499-507. PubMed DOI

Cerqueira TLO, Ramos YR, Strappa GB, De Jesus MS, Santos JG, Sousa C, et al. Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis. Arch Endocrin Metab. 2018 Aug 1;62(4):466-71. PubMed DOI