Endocrine Abstracts

Objectives: The interaction between genetic predisposing factors and environmental triggers is crucial for the development of HT. In last decades, the steady rise in frequency of HT in developed countries pointed to a strong influence of changing environmental factors, including increased pollution. Air pollutants, like dioxins and polycyclic aromatic hydrocarbons, are ligands of the aryl hydrocarbon receptor (AHR). This ligand-activated transcription factor, involved in pollutants detoxification, is a key modulator of anti-oxidant defences and immune responses, acting as a regulator of T-reg and Th17 cell differentiation. Aim of this study was to investigated if AHR polymorphisms may contribute to the genetic susceptibility to HT.

Patients and Methods: We evaluated the presence/distribution of specific and characterized polymorphisms of AHR gene, rs2066853 in exon 10 and rs10249788 in the promoter region, in 100 unrelated HT patients (90 F; mean age 50 ± SD 17 yr) and 100 unrelated sex- and age-matched healthy controls (HC). The sample size was estimated considering a power of 0.8 and an alpha value of 0.05. All subjects were caucasian non-immigrant, born and stably living in the same geographic area, including a high polluted area hosting a petrochemical complex and not-polluted rural and coastal areas. DNA was extracted from whole blood of each subject. The genotyping of AHR gene was performed by means of Restriction Fragment Length Polymorphism (RFLP) assay and nucleotide sequencing analysis. For all DNA datasets, genotype frequencies were in Hardy–Weinberg equilibrium.

Results: The polymorphism rs2066853 (G>A) was found in 2 HT patients in heterozygous condition, and in no HC. The SNP rs10249788 (C>T) was identified in 20/100 HT patients and in 8/100 HCs (all heterozygous C/T). The SNP frequency distribution was significantly different between HT patients and HCs (P < 0.05), and the OR value (>3) of heterozygous (C/T) genotype showed a significant correlation with the disease (P < 0.05). Statistical analysis of covariate variables demonstrated the SNP rs10249788 (C>T) was significantly and independently associated with family history of HT and thyroid function (P < 0.05). Noteworthy when evaluating its frequency distribution with respect to the area of residence, we found a significant difference between patients residing in areas with environmental issues and those living in non-polluted areas of the same province (P < 0.05).

Conclusions: We provide the first evidence that the SNP rs10249788 (C>T) is associated to Hashimoto’s thyroiditis, showing a significant correlation with exposure to environmental pollutants. AHR polymorphisms could contribute to genetic susceptibility to HT, modulating AHR expression.