Unit:
Τομέας ΠαθολογίαςLibrary of the School of Health Sciences
Dissertation committee:
Αλεβιζάκη Μαρία, Καθηγήτρια, Ιατρική, ΕΚΠΑ
Τουμανίδης Σάββας, Καθηγητής, Ιατρική, ΕΚΠΑ
Καλτσάς Γρηγόριος, Καθηγητής, Ιατρική, ΕΚΠΑ
Μητράκου Ασημίνα, Αναπλ. Καθηγήτρια, Ιατρική, ΕΚΠΑ
Λαμπρινουδάκη Ειρήνη, Αναπλ. Καθηγήτρια, Ιατρική, ΕΚΠΑ
Κασσσή Ευανθία, Αναπλ. Καθηγήτρια, Ιατρική, ΕΚΠΑ
Σταματελόπουλος Κίμων, Επίκ. Καθηγητής, Ιατρική, ΕΚΠΑ
Original Title:
Χρόνια αυτοάνοση θυρεοειδίτιδα: διατροφικοί παράγοντες και παράμετροι οξειδωτικού stress που επηρεάζουν την εξέλιξη της.
Translated title:
Autoimmune thyroiditis: nutrition factors and oxidative stress parameters associated with disease progression
Summary:
Hashimoto’s thyroiditis is the most common autoimmune thyroid disease and the main cause of hypothyroidism. It affects people of any age with an increased incidence in middle-aged women. Both genetic and environmental factors are implicated in the pathogenesis and the development of this disease. Thyroid gland normally produces moderate amounts of reactive oxygen species, which are necessary for thyroid hormone synthesis. Previous studies have shown that patients with Hashimoto's thyroiditis have elevated oxidative stress levels, even when they are euthyroid. Oxidative stress is associated with advanced glycation end products (AGEs) since both hyperglycemia and increased levels of oxidative stress increase the production of AGEs. Nutrition affects both oxidative stress and AGEs levels. AGEs’ effect is enhanced by binding to the RAGE receptor. Polymorphisms of the RAGE receptor gene, -429T>C and -374T>A, are involved in a wide range of diseases. So far, no similar studies have examined the role of these polymorphisms in autoimmune thyroid disease.
The aim of the present study was to investigate the effect of oxidative stress and nutrition on the development and the progression of Hashimoto's thyroiditis, in euthyroid women with Hashimoto's thyroiditis. Moreover, the distribution and the possible role of the two common polymorphisms of the RAGE gene, -429T>C and -374T>A, in Hashimoto’s thyroiditis were examined.
The study involved 317 euthyroid women 19 - 69 years old. The participants with Hashimoto’s thyroiditis (HT) were classified into two groups: the “HT with treatment” group consisted of 102 women on T4 replacement and the “HT without treatment” group consisted of 116 women who did not receive thyroxine treatment. The control group consisted of 99 women with no thyroid disease. To evaluate oxidative stress, total lipid peroxide levels (TOS) in serum were measured. Genotyping was performed to study the presence of -429T>C and -374T>A polymorphisms in the RAGE gene.
The results of this study showed that women with HT, particularly those on T4 replacement (x2=6.85, df=2, p=0.032) had an increased frequency of the
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polymorphism -429 T>C of the RAGE receptor gene. The frequency of the polymorphism -374T>A did not differ among the studied groups. The levels of oxidative stress were significantly elevated in the “HT with treatment” group compared to the “HT without treatment” and the control group (Mann-Whitney test, p<0.05). Further analysis demonstrated that TOS levels higher than 590 μmol/L in euthyroid women with HT are associated with an increased risk to develop hypothyroidism (OR=2.9). This risk is further increased in the carriers of the RAGE -429T>C polymorphism (OR=5.4).
Moreover, correlation between BMI values and TOS levels was observed (r=0.265, p<0.01). The participants were classified into three groups based on BMI values (normal weight, overweight, obese) and the percentage of women with high TOS levels (TOS≥590 μmol/L) was found to be higher in the obese group (x2=17.0, df=2, p<0.01). Further analysis showed that BMI value above 24.9 Kg/m2 is associated with an increased risk of high TOS levels (OR=2.9). Furthermore, women suffering from insomnia had increased risk of having high TOS levels (OR=2.7). A similar association was observed between nutrition and oxidative stress since limited consumption of fruits (<2 servings per day) and tea (<2 to 3 cups a week) appeared to increase the risk of high TOS levels (OR=2.6, OR=1.8 respectively). Logistic regression analysis showed that all these factors had a significant effect on the levels of TOS and were independent of each other.
In conclusion, our study suggests that both oxidative stress and the polymorphism -429T>C of the RAGE receptor contribute to the development and progression of Hashimoto’s thyroiditis. Behaviors such as maintaining a BMI within the normal range, getting sufficient hours of night sleep, consuming fruits more than 2 servings per day and tea more than 3 cups a week, all contribute in maintaining oxidative stress at low levels.
Main subject category:
Health Sciences
Keywords:
Hashimoto's thyroiditis, Oxidative stress, RAGE receptor, RAGE polymorphisms, Autoimmunity
Number of references:
195
