GSTO2*N142D gene polymorphism associated with hypothyroidism in Italian patients
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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.
KeywordsGSTs Hypothyroidism Oxidative stress Ascorbate Arsenic
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).
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