ASSESSMENT OF THE ROLE OF THYROID PEROXIDASE GENE POLYMORPHISM AS A CAUSE OF HYPOTHYROIDISM IN ZAGAZIG UNIVERSITY HOSPITAL PATIENTS

Abstract

Background: Thyroid peroxidase (TPO) is the main enzyme involving the thyroid hormone biosynthesis. Thus studying its gene mutation explains some of etiological factors of chronic autoimmune hypothyroidism. The changes in enzyme built structure due to gene polymorphism may stimulate autoantibody production that may cause thyroid destruction. Thus, we correlate the TPO gene mutation with anti TPO-ab serum levels.
Subjects and Methods: 25 participants from Zagazig University hospital were recruited in patient group with elevated serum TSH, low serum fT4 and positive anti TPO-ab level and history of hypothyroidism. 25 healthy subjects were recruited in control group. Two genetic variants in TPO gene -Thr725Pro of exon 12 and Arg386His of exon 8- were genotyped in both groups using polymerase chain reaction–restriction fragment length polymorphism technique. BsaJI and SacII restriction enzymes were used on the PCR products, respectively.
Results: The carriage of Pro allele (in Thr725Pro polymorphism of exon 12 of TPO gene), probably increased the susceptibility of autoimmune hypothyroidism (OR = 2.471, 95% CI = 1.100-5.547, and P = 0.027). Also, the carriage of Pro allele significantly increase the anti TPO-ab serum levels (P<0.0001). On the other hand, patients with His allele (in Arg386His in exon 8 of TPO gene), showed lower susceptibility to autoimmune hypothyroidism with no significant association with anti TPO-ab levels. Conclusion: This study found an association of Thr725Pro of exon 12 of TPO gene polymorphism with autoimmune hypothyroidism in Egyptians and correlated the anti-TPO-ab levels with different genotypes in hypothyroid patients. Also, it found no association of Arg386His of exon 8 of TPO gene with autoimmune hypothyroidism, and no relation was found between the anti TPO-ab levels in hypothyroid patients and its different genotypes in Egyptian population. Key words: Autoimmune – Hypothyroidism - Hashimoto's disease - Anti-TPO - Gene polymorphism - TPO gene - Thr725Pro -Arg386His