Molecular Biology Reports

, Volume 40, Issue 2, pp 1967–1971 | Cite as

GSTO2*N142D gene polymorphism associated with hypothyroidism in Italian patients

  • Sara Piacentini
  • Paola Maria Monaci
  • Renato Polimanti
  • Dario Manfellotto
  • Maria Fuciarelli
Article

Abstract

Hypothyroidism is a multifactorial endocrinal disease characterized by abnormally low thyroid hormone production. Thyroiditis is one of the primary causes of hypothyroidism, as it is an increasing level of inflammation in the thyroid gland that could be due to a failure of the anti-inflammatory response. Glutathione S-transferases are biomarkers of inflammation and oxidative stress. These phase II enzymes play a relevant role in detoxifying xenobiotic compounds. Particular attention has been focused on GSTA1, GSTM1, GSTO2, GSTP1, and GSTT1 genes to evaluate if GST gene polymorphisms are associated with hypothyroidism. We screened a case–control population (patients with hypothyroidism n = 110, controls n = 122) to analyze GST gene polymorphisms. GST SNPs were determined using the PCR–RFLP method, while GST null polymorphisms were determined using a Multiplex PCR. In this study, we found differences in genotype distribution between hypothyroid individuals and controls only for the GSTO2*N142D polymorphism. Logistic regression analysis, after adjustment for age and sex, confirmed this positive association (OR = 4.56; 95 % CI 1.22–17.00; p = 0.009). The GSTO2 enzyme can catalyze several reactions important for countering oxidative stress: subjects with the D142 allele may have a deficiency in the antioxidant enzymatic system. A decrease in antioxidant capacity may trigger increased oxidative stress. Previous studies have highlighted the role of GST enzymes in inflammation disorders, but no data are available on their role in hypothyroidism. Our results suggest that GSTO2 could increase disease risk susceptibility and could act as a risk factor for hypothyroidism in Italian patients.

Keywords

GSTs Hypothyroidism Oxidative stress Ascorbate Arsenic 

Notes

Acknowledgments

The authors thank the volunteer participants for their generous co-operation and the collaborators of the Clinical Endocrinology Laboratory of the “Ospedale Civile” of Tricarico, Matera. This research was supported by a grant from the University of Rome Tor Vergata (RSA 2009) to M.F. and by MIUR grant (PRIN 2009–2011, Prot. No. 200975T9EW).

References

  1. 1.
    Coria MJ, Pastrán AI, Gimenez MS (2009) Serum oxidative stress parameters of women with hypothyroidism. Acta Biomed 80:135–139PubMedGoogle Scholar
  2. 2.
    Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, Chiusano E, John R, Guaraldo V, George LM, Perona M, Dall’Amico D, Parkes AB, Joomun M, Wald NJ (2012) Antenatal thyroid screening and childhood cognitive function. N Engl J Med 366:493–501PubMedCrossRefGoogle Scholar
  3. 3.
    Erdamar H, Demirci H, Yaman H, Erbil MK, Yakar T, Sancak B, Elbeg S, Biberoğlu G, Yetkin I (2008) The effect of hypothyroidism, hyperthyroidism, and their treatment on parameters of oxidative stress and antioxidant status. Clin Chem Lab Med 46:1004–1010PubMedCrossRefGoogle Scholar
  4. 4.
    Chakera AJ, Pearce SH, Bijay V (2012) Treatment for primary hypothyroidism: current approaches and future possibilities. Drug Des Dev Ther 6:1–11Google Scholar
  5. 5.
    Dursun B, Dursun E, Capraz I, Ozben T, Apaydin A, Suleymanlar G (2008) Are uremia, diabetes, and atherosclerosis linked with impaired antioxidant mechanisms? J Investig Med 56:545–552PubMedGoogle Scholar
  6. 6.
    Duntas LH (2005) Oxidants, antioxidants in physical exercise and relation to thyroid function. Horm Metab Res 37:572–576PubMedCrossRefGoogle Scholar
  7. 7.
    Asayama K, Dobashi K, Hayashibe H, Megata Y, Kato K (1987) Lipid peroxidation and free radical scavengers in thyroid dysfunction in the rat: a possible mechanism of injury to heart and skeletal muscle in hyperthyroidism. Endocrinology 121:2112–2118PubMedCrossRefGoogle Scholar
  8. 8.
    Venditti P, Balestrieri M, Di Meo S, De Leo T (1997) Effect of thyroid state on lipid peroxidation, antioxidant defences, and susceptibility to oxidative stress in rat tissues. J Endocrinol 155:151–157PubMedCrossRefGoogle Scholar
  9. 9.
    Das K, Chainy GB (2001) Modulation of rat liver mitochondrial antioxidant defence system by thyroid hormone. Biochim Biophys Acta 1537:1–13PubMedCrossRefGoogle Scholar
  10. 10.
    Petrovic N, Cvijic G, Davidovic V (2001) The activity of antioxidant enzymes and the content of uncoupling protein-1 in the brown adipose tissue of hypothyroid rats: comparison with effects of iopanoic acid. Physiol Res 50:289–297PubMedGoogle Scholar
  11. 11.
    Araujo ASR, Seibel FER, Oliveira UO, Fernandes T, Liesuy S, Kucharski L, Belló-Klein A (2011) Thyroid hormone-induced haemoglobin changes and antioxidant enzymes response in erythrocytes. Cell Biochem Funct 29:408–413PubMedCrossRefGoogle Scholar
  12. 12.
    Polimanti R, Piacentini S, Fuciarelli M (2011) HapMap-based study of human soluble glutathione S-transferase enzymes: the role of natural selection in shaping the single nucleotide polymorphism diversity of xenobiotic-metabolizing genes. Pharmacogenet Genomics 21:665–672PubMedCrossRefGoogle Scholar
  13. 13.
    Polimanti R, Piacentini S, Lazzarin N, Re MA, Manfellotto D, Fuciarelli M (2011) Glutathione S-transferase variants as risk factor for essential hypertension in Italian patients. Mol Cell Biochem 357:227–233PubMedCrossRefGoogle Scholar
  14. 14.
    Piacentini S, Polimanti R, Porreca F, Martínez-Labarga C, De Stefano GF, Fuciarelli M (2011) GSTT1 and GSTM1 gene polymorphisms in European and African populations. Mol Biol Rep 38:1225–1230PubMedCrossRefGoogle Scholar
  15. 15.
    Piacentini S, Polimanti R, Squitti R, Ventriglia M, Cassetta E, Vernieri F, Rossini PM, Manfellotto D, Fuciarelli M (2012) GSTM1 null genotype as risk factor for late-onset Alzheimer’s disease in Italian patients. J Neurol Sci 317:137–140PubMedCrossRefGoogle Scholar
  16. 16.
    Polimanti R, Piacentini S, Lazzarin N, Vaquero E, Re MA, Manfellotto D, Fuciarelli M (2012) Glutathione S-transferase genes and the risk of recurrent miscarriage in Italian women. Fertil Steril 98:396–400Google Scholar
  17. 17.
    Piacentini S, Polimanti R, Moscatelli B, Re MA, Fuciarelli R, Manfellotto D, Fuciarelli M (2010) Glutathione S transferase gene polymorphisms and air pollution as interactive risk factors for asthma in a multicenter Italian field study: a preliminary study. Ann Hum Biol 37:427–439PubMedCrossRefGoogle Scholar
  18. 18.
    Piacentini S, Polimanti R, Moscatelli B, Re MA, Manfellotto D, Fuciarelli M (2012) Lack of association between GSTM1, GSTP1 and GSTT1 gene polymorphisms and asthma in adult patients from Rome (Central Italy). J Investig Allergol Clin Immunol 22:252–256PubMedGoogle Scholar
  19. 19.
    Schmuck EM, Board PG, Whitbread AK, Tetlow N, Cavanaugh JA, Blackburn AC, Masoumi A (2005) Characterization of the monomethylarsonate reductase and dehydroascorbate reductase activities of Omega class glutathione transferase variants: implications for arsenic metabolism and the age-at-onset of Alzheimer’s and Parkinson’s diseases. Pharmacogenet Genomics 15:493–501PubMedCrossRefGoogle Scholar
  20. 20.
    Linster CL, Van Schaftingen E (2007) Vitamin C. Biosynthesis, recycling and degradation in mammals. FEBS J 274:1–22PubMedCrossRefGoogle Scholar
  21. 21.
    Menashe I, Rosenberg PS, Chen BE (2008) PGA: power calculator for case–control genetic association analyses. BMC Genet 9:36PubMedCrossRefGoogle Scholar
  22. 22.
    Polimanti R, Piacentini S, Porreca F, Fuciarelli M (2010) Glutathione S-transferase ω class (GSTO) polymorphisms in a sample from Rome (Central Italy). Ann Hum Biol 37:585–592PubMedCrossRefGoogle Scholar
  23. 23.
    Pasupathi P, Latha R (2008) Free radical activity and antioxidant defense mechanisms in patient with hypothyroidism. Thyroid Sci 3:1–6Google Scholar
  24. 24.
    Haldimann M, Alt A, Blanc A, Blondeau K (2005) Iodine content of food groups. J Food Comp Anal 18:461–471CrossRefGoogle Scholar
  25. 25.
    Åsvold BO, Bjøro T, Nilsen TIL, Vatten LJ (2007) Tobacco smoking and thyroid function. A population-based study. Arch Intern Med 167:1428–1432PubMedCrossRefGoogle Scholar
  26. 26.
    Sturchio E, Minoia C, Zanellato M, Masotti A, Leoni E, Sottani C, Biamonti G, Ronchi A, Casorri L, Signorini S, Imbriani M (2009) Interferenti endocrini. Schede monografiche: arsenico. G Ital Med Lav Erg 31:5–32Google Scholar
  27. 27.
    Board PG (2011) The omega-class glutathione transferases: structure, function, and genetics. Drug Metab Rev 43:226–235PubMedCrossRefGoogle Scholar
  28. 28.
    Whitbread AK, Masoumi A, Tetlow N, Schmuck E, Coggan M, Board PG (2005) Characterization of the omega class of glutathione transferases. Meth Enzymol 401:78–99PubMedCrossRefGoogle Scholar
  29. 29.
    Deshpande UR, Joseph LJ, Patwardhan UN, Samuel AM (2002) Effect of antioxidants (vitamin C, E and turmeric extract) on methimazole induced hypothyroidism in rats. Indian J Exp Biol 40:735–738PubMedGoogle Scholar
  30. 30.
    Block G, Shaikh N, Jensen CD, Volberg V, Holland N (2011) Serum vitamin C and other biomarkers differ by genotype of phase 2 enzyme genes GSTM1 and GSTT1. Am J Clin Nutr 94:929–937PubMedCrossRefGoogle Scholar
  31. 31.
    Davey JC, Nomikos AP, Wungjiranirun M, Sherman JR, Ingram L, Batki C, Lariviere JP, Hamilton JW (2008) Arsenic as an endocrine disruptor: arsenic disrupts retinoic acid receptor- and thyroid hormone receptor-mediated gene regulation and thyroid hormone-mediated amphibian tail metamorphosis. Environ Health Perspect 116:165–172PubMedCrossRefGoogle Scholar
  32. 32.
    Cubadda F, Ciardullo S, D’Amato M, Raggi A, Aureli F, Carcea M (2010) Arsenic contamination of the environment–food chain: a survey on wheat as a test plant to investigate phytoavailable arsenic in Italian agricultural soils and as a source of inorganic arsenic in the diet. J Agric Food Chem 58:10176–10183PubMedCrossRefGoogle Scholar
  33. 33.
    Polimanti R, Piacentini S, De Angelis F, De Stefano GF, Fuciarelli M (2011) Human GST loci as markers of evolutionary forces: GSTO1*E155del and GSTO1*E208K polymorphisms may be under natural selection induced by environmental arsenic. Dis Markers 31:231–239PubMedGoogle Scholar
  34. 34.
    Piacentini S, Polimanti R, Squitti R, Mariani S, Migliore S, Vernieri F, Rossini PM, Manfellotto D, Fuciarelli M (2012) GSTO1*E155del polymorphism associated with increased risk for late-onset Alzheimer’s disease: association hypothesis for an uncommon genetic variant. Neurosci Lett 506:203–207PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Sara Piacentini
    • 1
  • Paola Maria Monaci
    • 1
  • Renato Polimanti
    • 1
  • Dario Manfellotto
    • 2
  • Maria Fuciarelli
    • 1
  1. 1.Department of BiologyUniversity of Rome “Tor Vergata”RomeItaly
  2. 2.Clinical Pathophysiology Center“San Giovanni Calibita” Fatebenefratelli Hospital, AFaRRomeItaly

Personalised recommendations