Endocrine Abstracts

Background: Circadian rhythmicity is generated by a set of genes including Period3. Changes in the expression of Period3 and other clock genes have been linked with regulation of the immune system. Period3 polymorphisms have been associated with circadian disruption and so immune system dysregulation and altered secretion of several cytokines, which can lead to inflammatory and autoimmune disorders.

Aim: To investigate the influence of a polymorphism in Period3 gene on susceptibility and severity of autoimmune thyroid diseases (AITD).

Methods: A total of 125 unrelated patients (mean age 35.94±9.9 years) with AITD (GD, 69; HT, 56) and 115 unrelated healthy controls (mean age 31.3±8.7 years) were included. Serum levels of IL-6 (pg/ml) and TNF-α (pg/ml) were determined by ELISA method. Period3 gene polymorphism rs2797685 was identified by PCR-RFLP.

Results: Subjects expressing the GA+AA genotype of the selected polymorphism in Period3 gene demonstrated a significantly higher risk of AITD compared to the population expressing the GG genotype (OR=1.83, CI: 1.04-3.20; P=0.033). No significant associations of genotypes were detected with the age of onset of disease, presence and severity of orbitopathy in GD and thyroid function status at diagnosis and daily dose of thyroxine per kg body weight in HT. AITD and control groups were similar in terms of mean IL-6 levels, but mean serum IL-6 level was significantly lower in the group with GA genotype than in the group with GG genotype in GD (P=0.013). Mean level of TNF-α was significantly higher in patients with AITD compared with controls (P<0.001) but TNF-α levels were not significantly different in the groups of different genotypes of the selected polymorphism of the Period3 gene.

Conclusion: This study provides the first evidence for a genetic association between AITD and the Period3 gene, highlighting the possible relevance of polymorphisms in clock genes in the etiopathogenesis of AITD.